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INSERT INTO `web_blogs` VALUES (1,'Knock In and Knock Out Mice as Powerful Disease Models','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/Screen-Shot-2020-03-03-at-12.png',' Why Do We Care About Gene-edited Mice? The generation of knockout and knock-in animal models has allowed not only disease research but also the development of disease-fighting drugs. The Nobel Prize for Physiology and Medicine recognized Evans, Smithies, and Capecchi for their joint effort in creating the first knockout mouse over two decades ago in <a href=\"https://www.nature.com/scitable/content/knockout-mice-timeline-6638351/\">1989</a>, with knock-in mice to follow. Continued interdisciplinary efforts have since built upon mouse knockout and knock-in methods to successfully study the function of genes, elucidate critical biological pathways, and create animal models for pressing human illnesses, such as neurodegeneration and cancer.As biotechnology rapidly advances forward, interest in using knockout and knock-in mice to model human disease has only grown. Allowing the regulation, either expression or repression, of both endogenous and exogenous genes, gene editing can be used either to study the mechanisms behind human disease or to test potential therapeutics. Because the studied protein coding regions of mouse and human genomes are roughly 85% identical, mouse models are often used (NIH, 2010). The benefits of using the knockout or knock-in mouse model to study disease include its endless applications and relative ease of manipulation. Knockout and Knock-in Technology Highlight: CRISPR/Cas9. Indeed, knockout and knock-in mouse models have been developed to both understand the mechanisms of diseases and discover drugs to treat them. The efficiency of generating knockout mice is significantly higher than that of knock-in mice, as there are many ways to disrupt the endogenous locus but fewer ways to effectively drive exogenous gene expression. To obtain gene edited mice, the CRISPR/Cas9 system is one of the preferred methods available. Offering a more refined product when compared to the random insertions of transgenesis, the CRISPR/Cas9 platform can create both knockout and knock-in mice in less time compared to the traditional mESC based homologous recombination approach. Biocytogen’s Extreme Genome Editing, <a href=\"https://biocytogen.com/gene-editing/by-technologies/crispr-ege-based-gene-editing/\">EGE</a>®, can knock in exceptionally large DNA fragments, increasing the application potential of knock-in animal models. Traditional Knockout Example: Multiple Sclerosis <a href=\"https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269\">Multiple Sclerosis</a> (MS) is an autoimmune disease that has been modeled through the animal model, <a href=\"https://biocytogen.com/preclinical-services/autoimmune-inflammation-diseases/eae-model/\">experimental autoimmune encephalomyelitis </a> (EAE). A potentially disabling disease, MS is diagnosed when the body attacks its own myelin sheath. When the cytokine, monocyte chemoattractant protein 1 (MCP-1), was knocked out it was discovered that these mice were “markedly resistant to EAE after active immunization” (Huang 2001). These results add to not just the existing understanding of immunogenetic functions, but they also shed light into a possibly critical component of autoimmune disease development. Notably, this MCP-1 knockout animal model was shown to have remarkably reduced clinical and histological effects on autoimmune neurodegeneration, indicating at the role MCP-1 plays in immune response and autoimmune disease induction (Huang, 2001). Conditional Knockin Example: Breast Cancer Representing 15% of all cancer cases, breast cancer is one of the most common cancers (NIH, 2019). One in five breast cancer cases will be HER2-positive, which are often more severe and aggressive (Moynihan, 2018). <a href=\"https://www.mayoclinic.org/breast-cancer/expert-answers/faq-20058066\">HER2</a> is a cell surface marker, also known as ERBB2, and it is overexpressed in HER2-positive tumor cells (Moynihan, 2018). To model breast cancer induction, numerous knock-in animal models have been generated to upregulate HER2 or the mouse orthologue Erbb2, many of which take advantage of strong viral promoters to constitutively drive expression. Not only is the HER2 mouse model used to elucidate disease progress, but it is also used in the various stages of drug validation (Fry, 2016).To more closely model the human breast cancer timeline, the Cre-Lox recombinase conditional gene targeting system was used on the oncogene Erbb2. In the lab, a Cre-inducible homologue of the first exon of Erbb2 was knocked-in. Upon inducing the recombinase, mammary-specific expression of activated Erbb2 was observed along with accelerated mammary epithelial development and subsequent tumor development. These data suggest that tumorigenesis requires “concerted amplification and overexpression of Erbb2 protein” (Andrechek, 2000). Targeted Knockout Example: Metastatic Cancer A recent example of CRISPR/Cas9 applied in oncology animal models is the mouse knockout of CD146. CD146 overexpression has been shown to be sufficient to induce malignant metastases (Ma, 2018). EMT, or epithelial to mesenchymal transition, is an evolutionarily conserved development process that also enhances metastatic properties such as mobility, invasion, and resistance to apoptotic stimuli in cancer cells (Sun, 2016). When CD146 was knocked out using a CRISPR/Cas9 based gene editing platform, the downregulation of regulative proteins of EMT was observed (Ma, 2018). The study demonstrated CD146’s role in driving cell progression into EMT, both in the embryonic development process and in cancer malignancy, identifying CD146 as a target in cancer treatment (Ma, 2018). Today, CRISPR/Cas9 can globally remove or add genes to the mouse genome, with high precision and efficacy (see Figure 1). Creating knockout and knock-in mice is a fundamental operation of many facilities, but the results take months at a minimum and do not carry a guarantee. Biocytogen’s mission is to help scientists to unlock the bottleneck by reducing their effort, as well as ensuring accurate study results using meticulously designed models.At Biocytogen, we offer a myriad of gene editing services, including knockout and knock-in animals. Using our <a href=\"https://biocytogen.com/gene-editing/by-technologies/crispr-ege-based-gene-editing/\">Extreme Genome Editing</a>, EGE®, technology, we can deliver a F1 heterozygous mouse line in six to eight months. The efficiency of homologous recombination mediated by the EGE® system is up to 20 times higher than conventional CRISPR/Cas9 technology, which makes gene editing with EGE® system faster and more feasible for complicated targeting design. EGE® system can edit the DNA sequence precisely at almost any genomic locus to achieve many types of desired model generation including global/conditional (c) mutation (m)/reporter knockin (KI), knockout (KO), cKO&cKI, and humanized gene KI, etc. Biocytogen also offers the best-in-class quality control protocol using Southern blot to ensure the successful delivery of each gene targeting project. You can <a href=\"https://biocytogen.com/animal-cell-models/\">browse</a> mouse models developed by Biocytogen that are currently available to order. <a href=\"https://biocytogen.com/contact-us/\">Contact us now</a> to request your custom gene-edited mice. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/CRISPR_Cas9.png\" style=\"height:525px; width:600px\" class=\"aligncenter wp-image-4459\" />(Figure 1. CRISPR/Cas9 Based Gene Editing. Using a guide sgRNA, the CRISPR/Cas9 gene editing platform identifies the specific sequence to be modified. That sequence is then “cut out” and replaced by an insertion gene. Image from Biocytogen)Works Cited:Andrechek, E. R., Hardy, W. R., Siegel, P. M., Rudnicki, M. A., Cardiff, R. D., & Muller, W. J. (2000). Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis. Proceedings of the National Academy of Sciences, 97(7), 3444–3449. doi: 10.1073/pnas.97.7.3444National Cancer Institute of the National Institute of Health. Cancer of the Breast (Female) - Cancer Stat Facts. (n.d.). Retrieved from Cancer of the Breast (Female) - Cancer Stat FactsFry, E. A., Taneja, P., & Inoue, K. (2016). Clinical applications of mouse models for breast cancer engaging HER2/neu. Integrative Cancer Science and Therapeutics, 3(5). doi: 10.15761/icst.1000210Huang, D., Wang, J., Kivisakk, P., Rollins, B. J., & Ransohoff, R. M. (2001). Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis. The Journal of Experimental Medicine, 193(6), 713–726. doi: 10.1084/jem.193.6.713Ma, Y., Zhang, H., Xiong, C., Liu, Z., Xu, Q., Feng, J., … Yan, X. (2018). CD146 mediates an E-cadherin-to-N-cadherin switch during TGF-β signaling-induced epithelial-mesenchymal transition. Cancer Letters, 430, 201–214. doi: 10.1016/j.canlet.2018.05.016Sun, T., Qin, Y., & Zhong, W.-L. (2016). Epithelial-Mesenchymal Transition and its Regulation in Tumor Metastasis. Tumor Metastasis. doi: 10.5772/64497Timothy J. Moynihan, M. D. (2018, November 2). What to know about HER2-positive breast cancer. Retrieved from <a href=\"http://www.mayoclinic.org/breast-cancer/expert-answers/faq-20058066\">http://www.mayoclinic.org/breast-cancer/expert-an</a>Why Mouse Matters. (n.d.). Retrieved from <a href=\"http://www.mayoclinic.org/breast-cancer/expert-answers/faq-20058066\">https://www.genome.gov/10001345/importance-of-mouse-genomeswers/faq-20058066</a>.',1,'/knock-in-and-knock-out-mice-as-powerful-disease-models',0,20,1583256976,2453,'us,jp,kr',1583256976,0),(2,'Gene Targeting Service Verified with Industry-leading Quality Control Measures','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/shutterstock_367760708.jpg',' At Biocytogen, we take pride in our quality control measures when we target and edit genes for our mouse models and drug development endeavors. From preventing potentially disastrous results before they occur to instituting reliable, tried-and-true protocols, proper attention to quality control when gene-editing can save clients both time and resources. For example, based on our internal data, the random insertion rate of gene-edited mice generated by CRISPR based EGE method is about 32%, and almost half of them can’t be segregated from the properly targeted allele through breeding. Quality control, we believe, is integral and vitally important not only in matters of quality assurance during the model production steps but also in the end-user application process. The standard procedures involved in the QCs may seem costly, labor-intensive and time-consuming, but it is absolutely rewarding from a long-term perspective. To discuss some aspects of quality control in gene editing, we would like to introduce you to two expertise, in-house scientists at Biocytogen: Min Deng, Ph.D. and Dan Wang, Ph.D. Who are you? Min Deng, Ph.D. (MD) was a research assistant professor and manager at the University of Rochester, specializing in neuroscience, development, transgenic and knockout technologies. At Biocytogen, Min is a senior scientist II and a senior project manager. She has more than 18 years of expertise in the production and application of gene-edited cell lines and rodent (mouse and rat) models. She is keen on anything related to biology. She likes music, travel and good food.Dan Wang, Ph.D. (DW) graduated from Cornell University and obtained postdoctoral training at Harvard Medical School, specializing in diabetic embryopathy, stem cell, and regenerative medicine. Upon joining Biocytogen, Dan has been building up the company’s expertise in genome editing and program management. Dan is a senior scientist providing targeting strategy designs and a project manager leveraging her technical expertise, scientific conceptual understanding, and management capacity to provide strategic support with total solutions to accommodate the researchers\' request. Dan thrives working in a dynamic environment by building multicultural teams as well as driving internal alignment and external collaborations. Can you describe a time where you experienced a troublesome situation that could have been prevented by better Quality Control? MD: I used to be a manager in the transgenic core at University of Rochester. When we first attempted to generate a floxed mouse model using CRISPR/Cas9 method, we didn’t test sgRNA activity in vitro. Instead of targeting vectors, we used DNA oligo as the DNA template. After performing several rounds of microinjection, even though we screened many gene-edited F0 pups, they all had indels.DW: Yes, we have experienced several challenging situations since the first utilization of our <a href=\"https://biocytogen.com/gene-editing/by-technologies/crispr-ege-based-gene-editing/\">CRISPR/Cas9-based EGE™ platform</a> in 2014. Due to the lack of a proficient QC system at the time, several models generated in the first batch were problematic. Undesired phenotypes were observed, which theoretically wouldn\'t be resulted from the designed gene manipulation itself, suggesting that undesired cuts or random integrations might have occurred. In response, we have reinforced and optimized the system since then by adding three important QC steps to correct the situation. We are quite confident that we can now deliver the models with premium quality for our collaborators. What are the Quality Control systems in place at Biocytogen? Biocytogen offers three important quality control systems when the CRISPR/Cas9-based EGE™ technology is applied: <ol><li>Southern blot analysis is performed during F1 mice screening to exclude the possibility of random integration - we only deliver F1 mice with a clean genetic background without random insertion issues. Our data showed that when the ES cell method is used for the preparation, the probability of random insertion is about 20%; if CRISPR/Cas9 is used, the probability of random insertion increases to 32%. This QC step is vitally important;</li><li>Two rounds of PCR and sequencing analysis are performed on F0 founder stage to screen out undesired genome edits; two rounds of PCR and sequencing analysis are performed on F1 generation to ensure the whole targeted region are correct, excluding the ones with undesired genome edits and keeping the ones with desired edits only;</li><li>Highly predicted off-target site screening is performed for F1 mice. For each targeting site, we design at least eight sgRNAs and test their activity in vitro using our UCA kit to determine one appropriate sgRNA with high specificity and high activity, which dramatically decreases off-target effects.</li></ol> What makes Quality Control at Biocytogen stand out? MD: For our improved CRISPR/Cas9 based EGE system, instead of an oligo DNA template, we co-inject the targeting vector DNA with Cas9 mRNA and sgRNA. The targeting vector includes 5’ and 3’ homologous arms (~ 1.5 kb) which reduce random insertion and off-target effects tremendously.DW: There are many things that make us stand out. If you want me to pick one, I would say the Southern blot analysis for F1 generation of mice generated by CRISPR/Cas9-based EGE™ technology. So far Southern blot analysis is the most effective way to exclude the F1 mice with random integration issues. Unfortunately, most other vendors either haven\'t realized that or could not afford to perform Southern blot analysis, which requires a substantial amount of know-how to master.Indeed, research has demonstrated that even in on-target mutagenesis cases, DNA breaks caused by CRISPR/Cas9 may result in large-scale deletions or other undesired results (Kosicki). Improvement in confirming on-target alleles of interest is still needed (Ayabe). Utilizing the lessons learned and wisdom gained from over a thousand completed past projects, our scientists are focused on providing our clients with the most up-to-date, innovative protocols, technologies, and strategies. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/CRISPR_Cas9-copy.png\" style=\"height:525px; width:600px\" class=\"wp-image-4651\" /> Figure 1. CRISPR/Cas9, while specific and precise in many cases, can also produce random insertions, deletions, and inversions. We believe Southern Blot is the most effective way to exclude these undesired results. Image from: Biocytogen.Biocytogen offers gene-editing services based on multiple modalities, including CRISPR/Cas9 Extreme Genome Editing (EGE™), ESC-based gene editing, and transgenic technology, all backed with our industry-leading quality control as a top priority. With a team of over 200 scientists in China in addition to those in Boston, MA USA, Biocytogen is a global, multi-cultural company that is well versed in collaboration and communication. You can find Biocytogen’s work in numerous <a href=\"https://biocytogen.com/publications/\">publications</a> in high profile journals such as Nature, J. of Immunology, and Oncogene. <a class=\"btn btn-secondary\" href=\"https://biocytogen.com/brochures/gene-editing-service-brochure/\">Download Gene Editing Services Brochure</a> <a class=\"btn btn-secondary\" href=\"https://biocytogen.com/gene-editing/by-strategies/\">Learn More about Target Strategies</a> Works CitedKosicki, M., Tomberg, K., & Bradley, A. (2018). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature biotechnology, 36(8), 765-771.Ayabe, S., Nakashima, K., & Yoshiki, A. (2019). Off-and on-target effects of genome editing in mouse embryos. Journal of Reproduction and Development, 65(1), 1-5.Updated March 16 2020.',1,'/gene-targeting-service-verified-with-industry-leading-quality-control-measures',0,30,1584025827,2096,'us,jp,kr',1584025827,0),(3,'Syngeneic Mouse Models and Humanized Immune-Checkpoint Mice','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/Screen-Shot-2020-06-17-at-3.png','Why do we need Syngeneic Mouse Models?To test potential immuno-oncology therapeutics in vivo, it is necessary to ensure that the disease model used has an intact immune system. Immunotherapeutics work with the body’s immune system to fight cancer cells. Often through inhibiting specific cell receptors called immune checkpoints, immunotherapeutics seek to bind to receptors that, when bound to its ligand, prevents an immune response from mounting. Thus, when inhibiting these receptors, the immune system’s regulatory functions can be manipulated to be more active and effective in eliminating or killing cancer cells.What are the benefits of Syngeneic Mouse Models?Because an intact immune system is necessary to test immune checkpoint inhibitors, immunocompetent syngeneic models are ideal. For these syngeneic models, an isolated murine tumor cell line is implanted into immunocompetent mice of the same strain or genetic background. Consistent use of the same strain prevents tumor rejection, allowing successful implantation of tumor cells that are recognized as “self” by the mouse. Syngeneic mouse models offer the benefits of low cost, convenience, and ease of use. Figure 1. Illustration of syngeneic mouse model.How do you work with Syngeneic Mouse Models?As an added benefit of choosing to use syngeneic models for research, syngeneic cell lines, when available, can be relatively inexpensive and easy to culture in a lab setting. The syngeneic tumor cells are then injected into the mice, which have 100% penetrance, at controlled time periods based on the experimental design and model. Are there any downsides to Syngeneic Mouse Models?A clear drawback to classic syngeneic mouse models is the limited <a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/\">tumor lines</a> available in mice compared to that of human patients (see patient-derived xenografts or PDX). Moreover it is important to consider that while mouse-derived tumors can be analogous to human cancers, it is not certain that the mouse immune response will readily translate to that of the human.Humanized Immune-Checkpoint Mice and Syngeneic Mouse ModelsMoving traditional syngeneic mouse models toward today’s relevant immuno-oncology targets, Biocytogen offers many humanized immune-checkpoint mouse models. Humanized immune-checkpoint mice are genetically engineered to express human immune checkpoint proteins, which allow the engraftment of wild type or humanized murine cell lines. Our humanized immune-checkpoint mice are carefully designed and generated to maintain biological functions and ensure more reliable drug validation. With humanized mice, in vivo efficacy evaluation of humanized immune checkpoint antibodies or inhibitors becomes even more reliable and dependable.<a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/\">See Humanized Immune-Checkpoint Mice</a>Figure 2. Illustration of Human Immune-Checkpoint Mice. Check out more of our animal and cell models:<table style=\"border-collapse: collapse; width: 100%; height: 377px;\"><tbody><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; text-align: center; height: 24px;\"><h5>Main Categories</h5></td><td style=\"width: 42.959%; text-align: center; height: 24px;\"><h5>Sub Categories</h5></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; text-align: center; height: 89px;\" rowspan=\"4\">Humanized animal models</td><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/\">Humanized Immune-Checkpoint Mice</a></td></tr><tr style=\"height: 17px;\"><td style=\"width: 42.959%; height: 17px; text-align: center;\"><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/\">Humanized Cytokine Mice</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; height: 24px; text-align: center;\"><a href=\"https://biocytogen.com/products/humanized-gpcr-mice/\">Humanized GPCR Mice</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; height: 24px; text-align: center;\"><a href=\"https://biocytogen.com/products/other-humanized-model/\">Other Humanized Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; height: 48px; text-align: center;\" rowspan=\"2\">Immunodeficient Models</td><td style=\"width: 42.959%; height: 24px; text-align: center;\"><a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">Immunodeficient mice (B-NDG background)</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; height: 24px; text-align: center;\"><a href=\"https://biocytogen.com/products/immunodeficient-mouse-models-non-b-ndg-background/\">Immunodeficient mouse models (non B-NDG background)</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; height: 96px; text-align: center;\" rowspan=\"4\">Tool Models</td><td style=\"width: 42.959%; height: 24px; text-align: center;\"><a href=\"https://biocytogen.com/products/reporter-models/\">Reporter Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/cre-mouse-rat-models/\">Cre Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/dtr-models/\">DTR Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/other-tool-models/\">Other Tool Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; text-align: center; height: 24px;\">Disease Mouse Models</td><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/induced-disease-model-mice/\">Disease Mouse Models</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; text-align: center; height: 48px;\" rowspan=\"2\">KO Mouse Models</td><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/ko-mouse-models/\">Drug Target Knockout Mice</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/other-knockout-mouse-models/\">Other Knockout Mice</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 23.7076%; text-align: center; height: 48px;\" rowspan=\"2\">Cell Lines</td><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/\">Humanized Tumor Cell Lines</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 42.959%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/other-cancer-cell-lines/\">Other Cancer Cell Lines</a></td></tr></tbody></table>',1,'/humanized-immune-checkpoint-mice-and-syngeneic-mouse-models',0,40,1592420553,1528,'us,jp,kr',1592420553,0),(4,'Team Building in the White Mountains','Employee Story','','','July 27, 2021 - Biocytogen Boston Corporation held a team-building retreat at the Grand View Mountain Resort in New Hampshire last week.The event, propelled by the extensive recent growth of the USA Team, offered the opportunity for employees to engage with new colleagues across all departments, participate in outdoor recreational activities, and enjoy the beautiful grounds of the resort. The event was kickstarted by an animated round of Pictionary and a lively axe-throwing competition. The evening was rounded out by updates and highlights from our scientific, business, and operation teams, a dinner social, and a campfire. For many employees, the event was a welcome change from several months of social distancing and limited in-person meetings. With vaccination rates rising, the team remains hopeful that more in-person events will resume as we head into the latter half of 2021. Overall, the team-building event was the perfect opportunity to reconnect, recharge, celebrate our successes, and set goals for the remainder of 2021.[embed] ',1,'/team-building-in-the-white-mountains',0,50,1627393821,445,'us,jp,kr',1627393821,0),(5,'2021 Highlights: Humanized Model Publications','Animal Models','','','We are proud to highlight our growing list of <a href=\"https://biocytogen.com/publications/\">publications</a> featuring off-the-shelf and customized mouse, rat, and cancer cell models in well-respected, high-impact journals. Featured below is a selection of publications throughout 2021 that used our humanized mouse models. Congratulations to our colleagues who have contributed to these exciting results!<h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf94-1bb-mice/\">Humanized B-h4-1BB Mice</a></h3>Hurov K, Lahdenranta J, Upadhyaya P, Haines E, Cohen H, Repash E, Kanakia D, Ma J, Kristensson J, You F, et al. BT7480, a novel fully synthetic Bicycle tumor-targeted immune cell agonist™ (Bicycle TICA™) induces tumor localized CD137 agonism. J Immunother Cancer. 2021 Nov;9(11):e002883. doi: 10.1136/jitc-2021-002883. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34725211/\">34725211</a>. Upadhyaya P, Lahdenranta J, Hurov K, Battula S, Dods R, Haines E, Kleyman M, Kristensson J, Kublin J, Lani R, et al. Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist. J Immunother Cancer. 2021 Jan;9(1):e001762. doi: 10.1136/jitc-2020-001762. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/33500260/\">33500260</a>.You G, Lee Y, Kang YW, Park HW, Park K, Kim H, Kim YM, Kim S, Kim JH, Moon D, et al. B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes. Sci Adv. 2021 Jan 15;7(3):eaax3160. doi: 10.1126/sciadv.aax3160. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/33523913/\">33523913</a>. Zhai T, Wang C, Xu Y, Huang W, Yuan Z, Wang T, Dai S, Peng S, Pang T, Jiang W, et al. Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer. J Immunother Cancer. 2021 Jun;9(6):e002131. doi: 10.1136/jitc-2020-002131. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34172514/\">34172514</a>. <h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-mice-plus/\">Humanized B-hPD-1 Mice</a></h3>Hong Y, Feng Y, Sun H, Zhang B, Wu H, Zhu Q, Li Y, Zhang T, Zhang Y, Cui X, et al. Tislelizumab uniquely binds to the CC\' loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage. FEBS Open Bio. 2021 Mar;11(3):782-792. doi: 10.1002/2211-5463.13102. Epub 2021 Feb 16. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/33527708/\">33527708</a>.Huang J, Liu D, Wang Y, Liu L, Li J, Yuan J, Jiang Z, Jiang Z, Hsiao WW, Liu H, et al. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy. Gut. 2021 May 18:gutjnl-2020-321031. doi: 10.1136/gutjnl-2020-321031. Epub ahead of print. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34006584/\">34006584</a>. <h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-l1-h4-1bb-mice/\">Humanized B-hPD-L1/h4-1BB Mice</a></h3>Jeong S, Park E, Kim HD, Sung E, Kim H, Jeon J, Kim Y, Jung UJ, Son YG, Hong Y, et al. Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade. J Immunother Cancer. 2021 Jul;9(7):e002428. doi: 10.1136/jitc-2021-002428. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34230109/\">34230109</a>. <h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-l1-hlag3-mice/\">Humanized B-hPD-L1/hLAG3 Mice</a></h3>Jiang H, Ni H, Zhang P, Guo X, Wu M, Shen H, Wang J, Wu W, Wu Z, Ding J, et al. PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. Oncoimmunology. 2021 Jun 24;10(1):1943180. doi: 10.1080/2162402X.2021.1943180. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34239776/\">34239776</a>.<h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-pd-l1-mice/\">Humanized B-hPD-1/hPD-L1 Mice</a></h3>Park JJ, Thi EP, Carpio VH, Bi Y, Cole AG, Dorsey BD, Fan K, Harasym T, Iott CL, Kadhim S, et al. Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1. Nat Commun. 2021 Feb 22;12(1):1222. doi: 10.1038/s41467-021-21410-1. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/33619272/\">33619272</a>. <h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htigit-mice/\">Humanized B-hTIGIT Mice</a> and <a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1htigit-mice/\">Humanized B-hPD-1/hTIGIT Mice</a></h3>Xiao Y, Chen P, Luo C, Xu Z, Li X, Liu L, Zhao L. Discovery of a novel anti PD-L1 X TIGIT bispecific antibody for the treatment of solid tumors. Cancer Treat Res Commun. 2021 Sep 27;29:100467. doi: 10.1016/j.ctarc.2021.100467. Epub ahead of print. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34598062/\">34598062</a>. <h3><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hsirpa-hcd47-mice/\">Humanized B-hSIRPA/hCD47 Mice</a></h3>Xu Z, Gao J, Yao J, Yang T, Wang D, Dai C, Ding Y. Preclinical efficacy and toxicity studies of a highly specific chimeric anti-CD47 antibody. FEBS Open Bio. 2021 Jan 15. doi: 10.1002/2211-5463.13084. Epub ahead of print. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/33449453/\">33449453</a>.<h3><a href=\"https://biocytogen.com/renmab-mouse/\">RenMabTM Mice</a></h3>Nie J, Xie J, Liu S, Wu J, Liu C, Li J, Liu Y, Wang M, Zhao H, Zhang Y, et al. Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants. Cell Discov. 2021 Jul 20;7(1):53. doi: 10.1038/s41421-021-00292-z. PMID: <a href=\"https://pubmed.ncbi.nlm.nih.gov/34285195/\">34285195</a>.',1,'/2021-highlights-humanized-model-publications',0,60,1638999530,545,'us,jp,kr',1638999530,0),(6,'First Half of 2022 Publications Highlight','Animal Models','','','Our off-the-shelf and custom <a href=\"https://biocytogen.com/animal-cell-models/\">animal and cell models</a> are advancing cutting-edge biomedical research every day. One measure of this impact is how often they appear in high impact <a href=\"https://biocytogen.com/publications/\">publications</a> and journals. Check out the list of studies published so far this year which feature Biocytogen models:<h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3e-mice/\">B-hCD3E Mice</a></h3>Zhang, R., Zhang, J., Zhou, X. et al. <a href=\"https://biocytogen.com/publications...ion-of-cd3e-humanized-mice-in-immunotherapy/\">The establishment and application of CD3E humanized mice in immunotherapy.</a> Exp Anim. (2022). <a href=\"https://doi.org/10.1538/expanim.22-0012\">The establishment and application of CD3E humanized mice in immunotherapy</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-mice/\">B-hPD-1 Mice</a></h3><a href=\"https://biocytogen.com/publications...med-cell-death-ligand-1-anti-pd-1-pd-l1-imm/\">Huang, J., Liu, D., Wang, Y. et al. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy.</a> Gut. (2021). <a href=\"http://dx.doi.org/10.1136/gutjnl-2020-321031\">http://dx.doi.org/10.1136/gutjnl-2020-321031</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-mice/\">Immunodeficient B-NDG Mice</a></h3>Mei, Z., Yang, T., Liu, Y. et al. Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment. Cell Rep Med. (2022). <a href=\"https://doi.org/10.1016/j.xcrm.2022.100608\">Redirecting</a>Huang, C.-S., Zhu, Y.-Q., Xu, Q.-C. et al. YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation. Clin Transl Med. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.1002/ctm2.848\" data-sheets-formula-bar-text-link=\"https://doi.org/10.1002/ctm2.848\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://doi.org/10.1002/ctm2.848</a>Shen, Y., Lu, C., Song, Z. et al. Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation. Nat Commun. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.1038/s41467-022-31141-6\">Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation - Nature Communications</a><h3><a class=\"waffle-rich-text-link\" href=\"https://renmab.com/\">RenMab Mice</a></h3>Chai, M., Guo, Y., Yang, L. et al. <a href=\"https://biocytogen.com/publications...es-targeting-the-highly-conserved-s2-domain/\">A high-throughput single cell-based antibody discovery approach against the full-length SARS-CoV-2 spike protein suggests a lack of neutralizing antibodies targeting the highly conserved S2 domain</a>. Brief Bioinform. (2022). <a href=\"https://doi.org/10.1093/bib/bbac070\">https://doi.org/10.1093/bib/bbac070</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hctla4-mice/\">B-hCTLA4 Mice</a></h3>Sato, Y., Casson, C.N., Matsuda, A. et al. Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy. Cancer Immunol Immunother. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.1007/s00262-022-03170-z\" data-sheets-formula-bar-text-link=\"https://doi.org/10.1007/s00262-022-03170-z\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://doi.org/10.1007/s00262-022-03170-z</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-l1-h4-1bb-mice/\">B-hPD-L1/h4-1BB Mice</a></h3>Muik, A., Garralda, E., Altintas, I. et al. Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors. Cancer Discov. (2022). <a href=\"https://doi.org/10.1158/2159-8290.CD-21-1345\">https://doi.org/10.1158/2159-8290.CD-21-1345</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-htnfr2/\">B-hTNFR2 Mice</a></h3>Chen, Y., Jia, M., Wang, S. et al. Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity. Front Immunol. (2022). <a class=\"waffle-rich-text-link\" href=\"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.835690/full\" data-sheets-formula-bar-text-link=\"https://doi.org/10.3389/fimmu.2022.835690\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">Frontiers | Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity</a><h3>B-hSTING Mice</h3>Ulrich-Lewis, J.T., Draves, K.E., Roe, K. et al. STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell-Dependent Antibody Responses. Front Immunol. (2022). <a class=\"waffle-rich-text-link\" href=\"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.861710/full\" target=\"_blank\" rel=\"noopener\" data-sheets-formula-bar-text-link=\"https://doi.org/10.3389/fimmu.2022.861710\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">Frontiers | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/products/genetically-modified-mice-rats/b-il17a-egfp-mice/\">B-Il17a-EGFP Mice</a></h3>Hu, B., Wang, H., Xiao, F. E74 Like ETS Transcription Factor 3 is a Negative Regulator of Pathogenic Lamina Propria T Helper 17.1 Cells in Murine Colitis. Immunol Invest. (2022). <a href=\"https://doi.org/10.1080/08820139.2022.2084409\">https://doi.org/10.1080/08820139.2022.2084409</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/efficacy-toxicity/\">Efficacy and Toxicity Studies</a></h3>Jiang, F., Shen, J., Cheng, J. et al. N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system. Sci Adv. (2022). <a href=\"https://doi.org/10.1126/sciadv.abm2343\">https://doi.org/10.1126/sciadv.abm2343</a><h3><a class=\"waffle-rich-text-link\" href=\"https://biocytogen.com/gene-editing/\">Gene Editing Services</a></h3>Hou, S., Li, Z., Dong, J. et al. Heterogeneity in endothelial cells and widespread venous arterialization during early vascular development in mammals. <a href=\"https://doi.org/10.1038/s41422-022-00615-z\">https://doi.org/10.1038/s41422-022-00615-z</a>Liu, C., Xiong, Q., Li, Q. et al. CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling. Nat Commun. (2022). <a href=\"https://doi.org/10.1038/s41467-022-29633-6\">https://doi.org/10.1038/s41467-022-29633-6</a>Li, S.L., Wang, Z.M., Xu, C. et al. Liraglutide Attenuates Hepatic Ischemia-Reperfusion Injury by Modulating Macrophage Polarization. Front Immunol. (2022). <a href=\"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.869050/full\" target=\"_blank\" rel=\"noopener\">https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.869050/full</a>Liu, C., Zhou, M., Jiang, W. et al. GPR105-Targeted Therapy Promotes Gout Resolution as a Switch Between NETosis and Apoptosis of Neutrophils. Front Immunol. (2022). <a href=\"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.870183/full\" target=\"_blank\" rel=\"noopener\">https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.870183/full</a>Li, S., Zhu, Q., Cai, Y. et al. Generation of an induced pluripotent stem cell line from a patient with Angelman syndrome carrying UBE3A mutation. Stem Cell Res. (2022).Xiong, X., Chen, S., Shen, J. et al. Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2. Sig Transduct Target Ther. (2022). <a href=\"https://doi.org/10.1038/s41392-022-00918-y\">https://doi.org/10.1038/s41392-022-00918-y</a>Li, J., Sun, X., You, Y. et al. Auts2 deletion involves in DG hypoplasia and social recognition deficit: The developmental and neural circuit mechanisms. Sci Adv. (2022).Wang, T., Xia, C., Weng, Q. et al. Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway. Haematologica. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.3324/haematol.2019.239186\" data-sheets-formula-bar-text-link=\"https://doi.org/10.3324/haematol.2019.239186\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://doi.org/10.3324/haematol.2019.239186</a>Jiang, K., Xu, Y., Wang, D. et al. Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis. Protein Cell. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.1007/s13238-020-00809-4\">https://doi.org/10.1007/s13238-020-00809-4</a>Liu, N., Tang, J., Xue, Y. et al. EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease. Aging Dis. (2022).Qian, L.L., Ji, J.J., Jiang, Y. et al. Serpina3c deficiency induced necroptosis promotes non-alcoholic fatty liver disease through β-catenin/Foxo1/TLR4 signaling. FASEB J. (2022).Zhang, Y., Ye, Y., Tang, X. et al. CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure. J Exp Med. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.1084/jem.20200418\" data-sheets-formula-bar-text-link=\"https://doi.org/10.1084/jem.20200418\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://doi.org/10.1084/jem.20200418</a>Dong, Z., Ma, Z., Yang, M. et al. The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy. J Inflamm Res. (2022).Cui, H.-Y., Wei, W., Qian, M.-R. et al. PDGFA-associated protein 1 is a novel target of c-Myc and contributes to colorectal cancer initiation and progression. Cancer Commun (Lond). (2022).Tian, C., Chai, J., Liu, W. et al. Role of the Demethylase AlkB Homolog H5 in the Promotion of Dentinogenesis. Front Physiol. (2022). <a class=\"waffle-rich-text-link\" href=\"https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.923185/full\" data-sheets-formula-bar-text-link=\"https://doi.org/10.3389/fphys.2022.923185\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.923185/full</a>Patel, P., Buchanan, C.N., Zdradzinski, M.D. et al. Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs. Nucleic Acids Res. (2022).Wang, J., Gong, J., Wang, Q. et al. VDAC1 negatively regulates melanogenesis through the Ca2+ - calcineurin-CRTC1-MITF pathway. Life Sci Alliance. (2022). <a class=\"waffle-rich-text-link\" href=\"https://doi.org/10.26508/lsa.202101350\" data-sheets-formula-bar-text-link=\"https://doi.org/10.26508/lsa.202101350\" data-sheets-formula-bar-text-style=\"font-size:16px;color:#1155cc;font-weight:normal;text-decoration:underline;font-family:\'\'docs-Calibri\'\';font-style:normal;text-decoration-skip-ink:none;\">https://doi.org/10.26508/lsa.202101350</a>',1,'/first-half-of-2022-publications-highlight',0,240,1659988825,512,'us,jp,kr',1659988825,0),(7,'2022 Popular Mouse Models and Cell Lines','Animal Models','','','Biocytogen’s advanced genome editing technologies have been leveraged by our own development scientists to create hundreds of animal and cell models used in biomedical research all over the world.13 years since our founding, Biocytogen’s catalog of off-the-shelf gene-edited animal models, BioMice, now contains more than 450 strains. From knock-outs to <a href=\"https://biocytogen.com/animal-cell-models/\">humanized knock-ins</a>, our models are ideal for preclinical evaluation of targeted therapeutics.If you’re looking for models to accelerate antibody discovery, our fully-human antibody mice, <a href=\"https://renmab.com/\">RenMice</a>，can spare critical months and costs. Our highly <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">immunodeficient</a> NDG model and its derivatives are superior for engraftment of human immune cells.Check out our most popular model and <a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/\">tumor cell Lines</a> list below!<table style=\"border-collapse: collapse; width: 100%; height: 722px;\"><tbody><tr style=\"height: 66px;\"><td style=\"width: 85.7305%; text-align: center; height: 66px;\" colspan=\"2\"><h4>Humanized Immune-Checkpoint Mice</h4></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"Name"}\">Name</td><td style=\"width: 65.443%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"Popularity"}\">Publications & Resources</td></tr><tr style=\"height: 107px;\"><td style=\"width: 20.2875%; height: 107px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-h4-1BB mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf94-1bb-mice/\">B-h4-1BB mice</a></td><td style=\"width: 65.443%; height: 107px;\" data-sheets-value=\"{"1":2,"2":"*****"}\">Publications: <a href=\"https://biocytogen.com/publications...entiated-cd8-tumor-infiltrating-lymphocytes/\">B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes</a><a href=\"https://biocytogen.com/publications...by-a-synthetic-tumor-targeted-cd137-agonist/\">Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist</a></td></tr><tr style=\"height: 45px;\"><td style=\"width: 20.2875%; height: 45px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hCD3E mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3e-mice/\">B-hCD3E mice</a></td><td style=\"width: 65.443%; height: 45px;\">Publications: <a href=\"https://biocytogen.com/publications...ion-of-cd3e-humanized-mice-in-immunotherapy/\">The establishment and application of CD3E humanized mice in immunotherapy</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hCD3EDG mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3edg-mice/\">B-hCD3EDG mice</a></td><td style=\"width: 65.443%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Webinar: <a href=\"https://biocytogen.com/webinar/advancing-t-cell-therapies-using-b-hcd3-mouse-models/\">Advancing T cell Therapies Using B-hCD3 Mouse Models</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hCD40 mice"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd40-mice/\">B-hCD40 mice</a></td><td style=\"width: 65.443%; height: 26px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd40-mice/\">Data package</a></td></tr><tr style=\"height: 109px;\"><td style=\"width: 20.2875%; text-align: center; height: 109px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd47-mice/\">B-hCD47 mice</a></td><td style=\"width: 65.443%; height: 109px;\">Publications: <a href=\"https://biocytogen.com/publications...ed-anti-tumor-activity-and-limited-toxicity/\">Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity</a><a href=\"https://biocytogen.com/publications...-dose-optimization-of-a-bispecific-antibody/\">Dose escalation PET imaging for safety and effective therapy dose optimization of a bispecific antibody</a></td></tr><tr style=\"height: 10px;\"><td style=\"width: 20.2875%; height: 10px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hPD-1 mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-mice/\">B-hPD-1 mice</a></td><td style=\"width: 65.443%; height: 10px;\" data-sheets-value=\"{"1":2,"2":"****"}\">Publications: <a href=\"https://biocytogen.com/publications...med-cell-death-ligand-1-anti-pd-1-pd-l1-imm/\">Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy</a><a href=\"https://biocytogen.com/publications...issociated-rate-and-complete-pd-l1-blockage/\">Tislelizumab uniquely binds to the CC’ loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage</a></td></tr><tr style=\"height: 51px;\"><td style=\"width: 20.2875%; height: 51px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hPD-1/hPD-L1 mice"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-pd-l1-mice/\">B-hPD-1/hPD-L1 mice</a></td><td style=\"width: 65.443%; height: 51px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Publications: <a href=\"https://biocytogen.com/publications...nternalization-of-programmed-death-ligand-1/\">Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1</a></td></tr><tr style=\"height: 51px;\"><td style=\"width: 20.2875%; height: 51px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hPD-1/hPD-L1/h4-1BB mice"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-h4-1bb-mice/\">B-hPD-1/hPD-L1/h4-1BB mice</a></td><td style=\"width: 65.443%; height: 51px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-h4-1bb-mice/\">Data package</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hPVRIG mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpvrig-mice/\">B-hPVRIG mice</a></td><td style=\"width: 65.443%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Poster: <a href=\"https://biocytogen.com/posters/aacr...l-for-evaluating-anti-pvrig-immunotherapies/\">Humanized PVRIG Mice: A Novel Tool for Evaluating Anti-PVRIG Immunotherapies</a></td></tr><tr style=\"height: 51px;\"><td style=\"width: 20.2875%; height: 51px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hSIRPA/hCD47 mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hsirpa-hcd47-mice/\">B-hSIRPA/hCD47 mice</a></td><td style=\"width: 65.443%; height: 51px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Publications: <a href=\"https://biocytogen.com/publications...highly-specific-chimeric-anti-cd47-antibody/\">Preclinical efficacy and toxicity studies of a highly specific chimeric anti-CD47 antibody</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hTIGIT mice"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htigit-mice/\">B-hTIGIT mice</a></td><td style=\"width: 65.443%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Publications: <a href=\"https://biocytogen.com/publications...iciting-nk-cell-mediated-antitumor-immunity/\">A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity.</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.2875%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-mice/\">B-hTREM2 mice</a></td><td style=\"width: 65.443%; height: 24px;\"> <a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-mice/\">Data package</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hVSIG4 mice"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hvsig4-mice/\">B-hVSIG4 mice</a></td><td style=\"width: 65.443%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Poster: <a href=\"https://biocytogen.com/posters/aacr...vsig4-antibodies-in-humanized-b-hvsig4-mice/\">Evaluating In Vivo Efficacy of Anti-VSIG4 Antibodies in Humanized B-hVSIG4 Mice </a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hOX40 mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf4ox40-mice/\">B-hOX40 mice</a></td><td style=\"width: 65.443%; height: 26px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf4ox40-mice/\">Data package</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.2875%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hLAG3 mice plus"}\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hlag3-mice-plus/\">B-hLAG3 mice plus</a></td><td style=\"width: 65.443%; height: 26px;\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hlag3-mice-plus/\">Data package</a></td></tr></tbody></table> <table style=\"border-collapse: collapse; width: 100%;\"><tbody><tr><td style=\"width: 85.7305%; text-align: center;\" colspan=\"2\"><h4>Immunodeficient Mice</h4></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 103px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-NDG B2m KO mice plus"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-b2m-ko-mice-plus-2/\">B-NDG B2m KO mice plus</a></td><td style=\"width: 65.5852%; height: 103px;\" data-sheets-value=\"{"1":2,"2":"*****"}\">Poster: <a href=\"https://biocytogen.com/posters/aacr...vl-immune-profiling-after-hpbmc-engraftment/\">Novel Engineered B-NDG B2M KO Mice Plus Shows Delayed GvHD response and Favorable GvL Immune Profiling After hPBMC Engraftment</a></td></tr><tr style=\"height: 26px;\"><td style=\"width: 20.1453%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-NDG hIL15 mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hil15-mice/\">B-NDG hIL15 mice</a></td><td style=\"width: 65.5852%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"*****"}\">Poster: <a href=\"https://biocytogen.com/posters/io-s...nt-after-human-pbmc-or-cd34-hsc-engraftment/\">B-NDG hIL-15 Mice Improve NK Cell Development After Human PBMC or CD34+ HSC Engraftment</a></td></tr></tbody></table> <table style=\"border-collapse: collapse; width: 100%;\"><tbody><tr><td style=\"width: 85.7305%; text-align: center;\" colspan=\"2\"><h4>Humanized Cytokine Mice</h4></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hIL2RA mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2ra-mice/\">B-hIL2RA mice</a></td><td style=\"width: 65.5852%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Publications: <a href=\"https://biocytogen.com/publications...ted-to-their-affinity-and-in-vitro-activity/\">Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hIL36R mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil36r-mice/\">B-hIL36R mice</a></td><td style=\"width: 65.5852%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"****"}\">Poster: <a href=\"https://biocytogen.com/posters/aacr...uation-of-therapeutic-drugs-targeting-il36r/\">Humanized IL36R Mice Provide a Preclinical Tool for the Evaluation of Therapeutic Drugs Targeting IL36R</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 51px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hIL4/hIL4RA mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil4-il4ra-mice/\">B-hIL4/hIL4RA mice</a></td><td style=\"width: 65.5852%; height: 51px;\" data-sheets-value=\"{"1":2,"2":"****"}\">Publications: <a href=\"https://biocytogen.com/publications...del-by-gene-editing-and-efficacy-evaluation/\">The establishment of humanized IL-4/IL-4RA mouse model by gene editing and efficacy evaluation</a></td></tr><tr style=\"height: 72px;\"><td style=\"width: 20.1453%; text-align: center; height: 72px;\"><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil6-hil6r-mice/\">B-hIL6/hIL6R mice</a></td><td style=\"width: 65.5852%; height: 72px;\">Poster: <a href=\"https://biocytogen.com/posters/aacr...idates-targeting-human-il6-and-il6-receptor/\">Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting human IL6 and IL6 receptor </a></td></tr></tbody></table> <table style=\"border-collapse: collapse; width: 100%;\"><tbody><tr><td style=\"width: 100%; text-align: center;\" colspan=\"2\"><h4>Humanized GPCR Mice</h4></td></tr><tr style=\"height: 77px;\"><td style=\"width: 23.5967%; height: 77px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hCCR8 mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hccr8-mice/\">B-hCCR8 mice</a></td><td style=\"width: 76.4033%; height: 77px;\" data-sheets-value=\"{"1":2,"2":"*****"}\">Poster: <a href=\"https://biocytogen.com/posters/aacr...r-anti-human-ccr8-antibody-drug-development/\">Humanized CCR8 Mouse Model Provides A Translational Tool For Anti-Human CCR8 Antibody Drug Development</a></td></tr></tbody></table> <table style=\"border-collapse: collapse; width: 100%; height: 166px;\"><tbody><tr style=\"height: 66px;\"><td style=\"width: 85.7305%; height: 66px;\" colspan=\"2\"><h4 style=\"text-align: center;\">Other Humanized Models</h4></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hCD38 mice"}\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hcd38-mice/\">B-hCD38 mice</a></td><td style=\"width: 65.5852%; height: 26px;\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hcd38-mice/\">Data package</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; height: 26px; text-align: center;\" data-sheets-value=\"{"1":2,"2":"B-hFcRn mice"}\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/other-humanized-model/b-hfcrn-mice/\">B-hFcRn mice</a></td><td style=\"width: 65.5852%; height: 26px;\" data-sheets-value=\"{"1":2,"2":"***"}\">Publications: <a href=\"https://biocytogen.com/publications...cy-in-il-23-induced-psoriasiform-dermatitis/\">IBI112, a selective anti-IL23p19 monoclonal antibody, displays high efficacy in IL-23-induced psoriasiform dermatitis. Int. Immunopharmacol</a><a href=\"https://biocytogen.com/publications...ces-antibody-directed-phagocytic-activities/\">A single-valent long-acting human CD47 antagonist enhances antibody directed phagocytic activities. Cancer Immunol. Immunother</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hher2-mice/\">B-hHER2 mice</a></td><td style=\"width: 65.5852%; height: 24px;\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hher2-mice/\">Data package</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 20.1453%; text-align: center; height: 24px;\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hpsma-mice/\">B-hPSMA mice</a></td><td style=\"width: 65.5852%; height: 24px;\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hpsma-mice/\">Data package</a></td></tr></tbody></table> <table style=\"border-collapse: collapse; width: 64.9582%; height: 162px;\"><tbody><tr style=\"height: 66px;\"><td style=\"width: 64.9596%; height: 66px;\" colspan=\"2\"><h4 style=\"text-align: center;\">Tumor Cell Lines</h4></td></tr><tr style=\"height: 24px;\"><td style=\"width: 32.9875%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hpd-l1-mc38/\">B-hPD-L1 MC38</a></td><td style=\"width: 31.9721%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hpd-l1-mc38/\">Data package</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 32.9875%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-hcd20-mc38/\">B-hCD20 MC38</a></td><td style=\"width: 31.9721%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-hcd20-mc38/\">Data package</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 32.9875%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-htrop2-mc38-plus/\"> B-hTROP2 MC38 plus </a></td><td style=\"width: 31.9721%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-htrop2-mc38-plus/\">Data package</a></td></tr><tr style=\"height: 24px;\"><td style=\"width: 32.9875%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/other-cancer-cell-lines/b-luc-hep-3b-plus/\">B-Luc Hep 3B plus</a></td><td style=\"width: 31.9721%; height: 24px;\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/other-cancer-cell-lines/b-luc-hep-3b-plus/\">Data package</a></td></tr></tbody></table>',1,'/2022-popular-mouse-models-and-cell-lines',0,250,1660244926,1050,'us,jp,kr',1660244926,0),(8,'Research Impact: Custom Biocytogen mouse models used to identify critical mediator of inflammation-driven metastases','Animal Models','bespoke,cancer,carcinogensis,custom,E3,HECTD3,invivo,ligase,metastasis,metastatic,model,mouse,murine,neoplasia,neoplastic,oncology,preclinical,research,studies,study,tumor,ubiquitin','https://cdn.biocytogen.com/web/backend/upload/article/image/shutterstock_1238322061.jpeg','By John Charpentier, Ph.D.September 7, 2022While metastases are ultimately responsible for <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745820/\">the large majority of cancer deaths</a>, most oncology drugs in development target primary tumors, and few specifically prevent metastasis. Although surgical resection of solid tumors is an effective early treatment intervention, the resulting inflammation can promote metastasis by increasing adhesion of circulating tumor cells (CTCs) to endothelial cells on distant organs.<a href=\"https://www.nature.com/articles/s41392-022-01057-0\">A new study</a> featuring Biocytogen mice has identified a critical mediator of inflammation-driven metastasis which may be suitable for future therapeutic development. Fubing Li and colleagues at the Chinese Academy of Sciences detailed their findings last month in the journal Signal Transduction and Targeted Therapy.<h4>A Ubiqiuitin Ligase Implicated in Metastasis</h4>The group focused on the E3 ubiquitin ligase HECTD3, which had been previously shown to drive chemotherapeutic resistance in some models via its ubiquitination of MALT1, Caspase-8, and Caspase-9. To investigate a potential role in inflammation-driven metastasis, Li et al. orthotopically transplanted mouse breast tumor cells into both wild-type and Hectd3-deficient mice. Two months after surgical resection of the primary tumors, they discovered significantly fewer lung and heart metastases in Hectd3-deficient mice compared to controls. Additionally, tumor-bearing mice lacking HECTD3 lived significantly longer, supporting a role for the protein in promoting metastatic death.To understand whether adhesion of CTCs to endothelial cells may be regulated by HECTD3 activity, Li and colleagues next performed genome-wide expression analysis in Hectd3-knock down human umbilical vein endothelial cells (HUVECs). The analysis identified dozens of target genes of the pleiotropic transcription factor NF-κB, including adhesion molecules and inflammatory mediators, that were downregulated in the knock-down cells relative to controls. Furthermore, global depletion of HECTD3 prevented inflammation-induced adhesion of tumor cells to endothelial cells both in vitro and in vivo.<h4>Custom Generated Mouse Models Demonstrate HECTD3\'s Role</h4>To rigorously evaluate the endothelial-specific role of HECTD3 in promoting metastasis in vivo, the team turned to Biocytogen. We designed, generated, and validated two genetically engineered mouse models enabling conditional alterations in HECTD3 expression: one permitting murine endothelial cell-specific knock-out of Hectd3 and another permitting HECTD3 over-expression in the same cells. Using these models, Li and colleagues showed that CTC colonization was significantly abrogated in the former case and significantly enhanced in the latter.Li’s group also characterized the mechanism by which HECTD3 activity drives metastasis: K63- and K-27-linked polyubiquitination at K296 of IKK-α (a.k.a. CHUK), a component of the IκB kinase complex regulating NF-κB. In the setting of post-surgical inflammation, this polyubiquitination activity prevents IKK-α degradation and results in its recruitment to adhesion molecule promoters, where it facilitates transcription.Biocytogen’s custom gene-edited rodent and cell models are being used every day to accelerate the pace of preclinical biomedical research. <a href=\"https://biocytogen.com/gene-editing/\">You can learn more about our various platforms for custom model generation here.</a>Citation: Li F, Liang H, You H, et al. Targeting HECTD3-IKKα axis inhibits inflammation-related metastasis. Signal Transduct Target Ther. 2022;7(1):264. Published 2022 Aug 3. doi:10.1038/s41392-022-01057-0',1,'/research-impact-custom-biocytogen-mouse-models-used-to-identify-critical-mediator-of-inflammation-driven-metastases',0,260,1662575012,604,'us,jp,kr',1662575012,0),(9,'Research Impact: B-NDG Mice Used to Identify Lipid Transport Mechanism Driving T Cell Leukemogenesis','Animal Models','AKT,B-NDG,cancer,immunodeficient,in vitro,in vivo,invitro,invivo,leukemia,leukemogenesis,lipid,lipids,lymphocyte,mTOR,NDG,neoplasia,neoplastic,NSG,oncogene,oncogenesis,OR4PL,OSBP,PI3K,preclinical,research,studies,study,T cell,T cells,T lymphocyte,tumor,tumorigenesis','https://cdn.biocytogen.com/web/backend/upload/article/image/or4pl_abstractdesign_v4.png','By John Charpentier, Ph.D.September 29, 2022 <a href=\"https://www.nature.com/articles/s41467-022-32104-7\">A recent study</a> featuring Biocytogen mice identifies a non-vesicular lipid transport mechanism required for T cell leukemogenesis. Wenbing Zhong and colleagues at Jinan University in Guangzhou, China report that a lipid binding protein called ORP4L, which is expressed in adult T cell leukemia (ATL) cells but not normal T cells, is critical for cell deterioration and oncogenesis. Altered Lipid Metabolism: A Hallmark of Cancer Dysregulation of lipid metabolism and altered membrane phosphoinositide dynamics have long been recognized as cellular hallmarks of cancer. In recent decades, much research has focused on how such changes contribute to reprogramming of intracellular signaling and energetic states and the evolution of malignancy. Hyperactivation of the PI3K/AKT/mTOR pathway, a master regulator of cell growth, metabolism, and proliferation, has been implicated in a wide variety of cancers, including leukemias. To sustain signaling through this pathway, cells require regular replenishment of a lipid precursor, phosphatidylinositol 4-phosphate (PI(4)P), at the plasma membrane. But how exactly pro-leukemic and leukemic T cells do this at rates sufficient to sustain their astonishing growth rates has thus far been unclear. A Lipid Transport Link to Oncogenic SignalingIn the absence of stimulation and ORP4L expression, PI(4)P is not shuttled to the plasma membrane and signaling through the PI3K-AKT-mTOR axis cannot be sustained (left). In the presence of stimulation and/or ORP4L expression, ORP4L heterodimerizes with OSBP to shuttle PI(4)P to the plasma membrane. There it enables pro-growth signaling through PI3K-AKT-mTOR, which contributes to leukemic transformation. For Zhong and his collaborators, the key was in understanding the activity of a lipid binding protein, ORP4L. In a series of in vitro experiments, they discovered that both PI(4)P and another lipid binding protein, OSBP, are transported from the Golgi apparatus to the plasma membrane following stimulation of T cells genetically engineered to express ORP4L. They then showed that OSBP heterodimerizes with ORP4L to shuttle PI(4)P between the Golgi apparatus and plasma membrane, supplying the precursor compound needed to maintain hyperactive PI3K/AKT/mTOR signaling. Next, the team demonstrated that ORP4L-OSBP-mediated PI(4)P plasma membrane delivery drives T cell deterioration and transformation in cell and animal models. They first transfected non-leukemic T cells with lentivirus encoding either wild-type ORP4L protein or a binding-incompetent variant, ORP4L△OSBP. After 16 weeks of culture, cells expressing wild-type ORP4L exhibited cellular phenotypes consistent with ATL, including high expression of Foxp3 and CCR4, IL-2-independent proliferation, and hyperactivation of the PI3K/AKT/mTOR pathway. Those expressing the version of ORP4L incapable of binding its OSBP partner, by contrast, died rapidly. ORP4L Promotes Leukemogenesis in Immunodeficient Mice To test whether the ORP4L-OSBP heterodimer performed the same function in vivo, Zhong and his colleagues turned to Biocytogen. Transplantation of ORP4L-expressing T cells into our <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">highly immunodeficient B-NDG mice</a> resulted in leukemic phenotypes and death of the mice within eight weeks. B-NDG mice transplanted with ORP4L△OSBP-expressing T cells, however, survived—powerful supporting evidence that ORP4L enables PI(4)P transport in vivo as well. Finally, when the team deleted ORP4L in transplanted ORP4L knock-in cells using a doxycycline-inducible CRISPR/Cas9 system, they observed significantly reduced tumor engraftment and prolonged survival, further evidence that ORP4L is critical component of a non-vesicular lipid transport mechanism required for T cell leukemogenesis. Biocytogen’s parental B-NDG strain and its dozens of derivative strains are setting a new standard for highly immunodeficient mouse models. B-NDG mice are exclusively distributed by <a href=\"https://www.envigo.com/model/nodcb17-prkdcscid-il2rgtm1-bcgenhsd\">Envigo</a>. Learn more about derived B-NDG strains, including humanized B-NDG mice <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">here</a>. You can check out more research publications featuring our mice <a href=\"https://biocytogen.com/publications/\">here</a>. Citation: Zhong W, Lin W, Yang Y, et al. An acquired phosphatidylinositol 4-phosphate transport initiates T-cell deterioration and leukemogenesis. Nat Comms. 2022;13(1):4390. doi:10.1038/s41467-022-32104-7Related blog: <a href=\"https://biocytogen.com/development-history-of-immunodeficient-mice-and-their-research-applications/\">Development History of Immunodeficient Mice and Their Research Applications</a>',1,'/research-spotlight-b-ndg-mice-used-to-identify-lipid-transport-mechanism-driving-t-cell-leukemogenesis',0,270,1664445621,630,'us,jp,kr',1664445621,0),(10,'Development History of Immunodeficient Mice and Their Research Applications','Animal Models','B2M KO,BALB/c,CDX,CSF1,ctla-4,dna-pkcs,foxn1,HLA,HLA-A2.1,HSCT,humanized,IL-15,IL-6,IL2rg,nod,NOD-scid,NOG,non-obese diabetic,NSG,nude,PDX,prkdc,rag1,rag2,SCID,ShiLTJ,sirpa,THPO,xenograft','https://cdn.biocytogen.com/web/backend/upload/article/image/flow_profiles.png','By John Charpentier, Ph.D.October 25, 2022<h4></h4>Since the characterization of the nude mouse in 1962, genetic mouse models of immunodeficiency have been increasingly developed, diversified, and utilized for both basic discovery research and preclinical studies of therapeutic candidates. Today, highly immunodeficient, genetically-engineered mouse models are invaluable tools for basic biomedical research, especially for the study of cancer, hematopoiesis, infectious diseases, and tissue regeneration. In addition to enabling in vivo studies in the absence of murine immune components, immunodeficient mice are ideal for human immune cell reconstitution and modeling of human immune responses.In this feature we will briefly review the history of immunodeficient mice, introduce and differentiate Biocytogen’s industry-leading immunodeficient <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-mice/\">B-NDG model</a>, and describe our latest advances in engineering next-generation strains within <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">the B-NDG family</a>. If you\'d prefer to view a video on this material, please see our recent webinar below.<iframe src=\"//www.youtube.com/embed/NntNxF6g7Hc\" width=\"560\" height=\"314\" allowfullscreen=\"allowfullscreen\"></iframe><h4>Why Use Immunodeficient Mouse Models?</h4>Highly immunodeficient mouse models enable the study of biological phenomena that are difficult or impossible to evaluate in other systems. Successful xenotransplantation of human cells or tissues, for example, is only feasible in a heterologous graft-tolerant model. This includes the in vivo reconstitution of human immune system components by engraftment of peripheral blood mononuclear cells (PBMCs) or CD34+ hematopoietic stem cells from whole blood donors.Broad humanization of the immune system in this manner makes tractable the study of human-like immune responses in the mouse and permits the evaluation of therapeutic candidates targeting or modulating them. Additionally, the abrogation of murine immunity enables the study of human-specific pathogens that would not otherwise productively infect rodents. Immunodeficient mice are also a powerful tool to assess the functional potential of embryonic and induced pluripotent stem cells.<h4>History of Immunodeficient Mouse Models</h4><h5>Nude mice</h5>The first genetic mouse model of immunodeficiency, the nude mouse, was discovered in 1962. These mice were characterized by a spontaneous deletion of Foxn1, a master regulator of the thymic epithelial cell lineage. In addition to producing their eponymous hairlessness, deletion of Foxn1 disrupts thymic architecture and inhibits the signal-dependent differentiation of thymocytes. Consequently, nude mice are athymic and lack mature T cells. While they are immunodeficient, nude mice do not efficiently tolerate patient-derived xenografts (PDXs) or cell-derived xenografts (CDXs).<h5>NOD mice</h5>Approximately two decades later, the non-obese diabetic (NOD)/ShiLTJ mouse was discovered. In contrast to nude mice, the NOD/ShiLTJ model is characterized by polymorphic Ctla-4 and Sirpα alleles. The latter encodes an inhibitory receptor that strongly binds human CD47 protein, and the former encodes a variant T cell immune checkpoint receptor with impaired functioning. These mice also exhibit a deficiency of the hemolytic complement component C5.Disruption of Ctla-4 results in unchecked pancreatic islet infiltration and destruction by lymphocytes, making the NOD mouse an early genetic model of Type I diabetes. The high-affinity binding of human CD47 by polymorphic Sirpα creates a more permissive environment in vivo for human-to-mouse xenografts. NOD mice are therefore more suitable for PDXs and CDX studies than nude mice, but engraftment efficiency remains quite low. Finally, loss of hemolytic complement impairs innate immunity by inhibiting chemotaxis of inflammatory myeloid cells and formation of the membrane attack complex (MAC).<h5>SCID mice</h5>The discovery of Rag1/2 and DNA-PKcs enzymes led to the generation of the severe combined immunodeficiency (SCID) model in 1985. Homozygous mutation of murine genes encoding these proteins severely impairs V(D)J recombination, an essential process for development of lymphocyte immunoreceptors. Consequently, SCID mice, which are congenic with the C.B-17 strain, have non-functional T and B cells and exhibit agammaglobulinemia. The presence of high numbers of murine NK cells, however, diminishes engraftment efficiency in in SCID mice, limiting their research application.<h5>NOD-SCID mice</h5>Transferring SCID mutations to the NOD background produced the NOD-SCID model, first characterized in 1990. These mice harbor mutations in both Ctla-4 and Prkdc (encoding a DNA-PKcs enzyme). As the name suggests, NOD-SCID mice exhibit defects in both innate and adaptive immunity seen in the parental strains and are much more suitable for PDX/CDX studies than either parental strain. These mice, however, have an elevated incidence of thymic lymphoma that shortens their average lifespan.<h5>IL2rγnull , NOG, and NSG™ mice</h5>In 1997, the IL-2rγnull mouse model, which carries a null allele of the IL-2 receptor common gamma (cγ) chain, was developed. As the cγ chain is a component of a number of cytokine receptors (i.e., IL-2/-4/-7/-9/-15/-21), these mice show profoundly impaired cytokine signaling and lymphocyte development. A major benefit of this model is the absence of murine NK cells, as IL-15 is required for NK cell ontogeny. The discovery of this model directly led to the further development of the highly immunodeficient models in use today, such as NOG and NSG™ mice, which were developed in the early 2000s. These mice lack Ctla-4, Prkdc, and have disrupted IL-2rγ function, resulting in severe defects in complement, cytokine signaling, and development of T, B, and NK cells.<h5>B-NDG mice</h5>Biocytogen’s highly immunodeficient B-NDG (NOD.CB17-PrkdcscidIl2rgtm1/Bcgen) mouse was engineered in 2014. Similar to NOG and NSG mice, these mice also lack Ctla-4 and Prkdc, and harbor a null Il2rγ allele. B-NDG mice eliminate some of the limitations of NOD-SCID immunodeficient mice, and do not exhibit variation in phenotypic penetrance, leakiness of disrupted murine genes, reduced longevity, or poor engraftment, proliferation, and functioning of xenotransplanted cells and tissues. B-NDG mice live much longer on average than NOD-SCID mice (18 vs. 8-9 months), likely due to the minimal incidence of thymic lymphoma. Leakage of murine lymphocytes in B-NDG mice is also negligible or absent in B-NDG mice, as detailed below.<h5>B-NDG Mice Lack T, B, and NK Cells</h5>B-NDG mice lack mature T, B, and NK cells. In the figure below, we see two representations of murine T, B, and NK cell populations isolated from 6 week old BALB/c, NOD-SCID, and B-NDG spleens (n = 3 females per group). On the top (A) we see representative flow cytometry plots showing the distribution of T, B, and NK cells among murine CD45+ cells in each model. The bottom panel (B) shows a quantitation of the same data. Note that while T and B cells are absent in both NOD-SCID and B-NDG mice, NK cells are only missing in the latter.<img class=\"aligncenter wp-image-29939\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/quant_flow_profiles.png\" alt=\"\" width=\"500\" height=\"334\" /><h5>Lymphoid Follicles Are Disrupted in B-NDG Mice</h5>Histological sections of lymphoid follicles from 9 week old, C57BL/6, NOD-SCID, and B-NDG mice show significant structural differences in the spleen and thymus. As shown in the spleen sections below, follicles in C57BL/6 mice are well-defined and exhibit normal morphology while follicles in NOD-SCID mice display white pulp hypoplasia and disordered follicles. B-NDG mice, on the other hand, show a total loss of follicular structure.<img class=\"aligncenter wp-image-29943\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/histo.png\" alt=\"\" width=\"750\" height=\"272\" /><h5>Circulating IgG and IgM Are Depleted in B-NDG mice</h5>As expected, B-NDG mice have dramatically reduced numbers of circulating IgG and IgM antibodies. Relative proportions of IgG and IgM in BALB/c and B-NDG mice were measured by ELISA and quantitated in the figure below. IgG and IgM concentrations in B-NDG mice were dramatically reduced compared to the BALB/c positive control and were essentially identical to negative controls. This trend was preserved across IgG subclasses.<img class=\"aligncenter wp-image-29942\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/igg.png\" alt=\"\" width=\"750\" height=\"292\" /><h5>Multiple Applications For B-NDG mice</h5>B-NDG mice are ideal for experiments using cell- and patient-derived xenografts (CDX/PDXs), as well as CAR studies. In the experiment summarized below, 5 × 106 Raji-Fluc B cells were transplanted into 8 B-NDG mice, and infused with 2 × 107 (human) CD19-targeting CAR-T cells or negative control 2 weeks later. In vivo bioluminescence imaging (BLI) shows limited expansion of tumor cells over 5 weeks in the post-infusion mice but not untreated control mice, who survived only three weeks following Raji-Fluc B cell transplantation.B-NDG mice are well-suited for human immune system reconstitution using PBMCs, CD34+ hematopoietic stem cells, or combined fetal bone marrow, liver, and thymus (BLT) transplant. In the experiment below, 5 × 106 human PBMCs were intravenously transplanted into 6 week old, female B-NDG mice (n = 6). Post-transplantation analysis revealed a high percentage of engrafted human CD45+ (hematopoietic) and human CD3+ T cells, as shown below. High levels of human T cell engraftment produces graft-versus-host effects responsible for the reduced body weight and decreased survival seen here.<h5></h5><h5>Next-Generation B-NDG Mouse Models</h5>Biocytogen scientists have further engineered the B-NDG model and developed a family of derived strains for broader research applications. One category of these next-generation models is B-NDG mice expressing transgenes to support human immune cell survival and differentiation.For example, <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hil6-mice/\">B-NDG hIL-6</a> mice show enhanced human B cell and plasma cell differentiation and expansion compared to the parental strain. Similarly, NDG hIL-15 mice support differentiation and proliferation of human lymphoid cells (NK, NKT, CD8+ T cells).The dually-humanized <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hcsf1-hthpo-mice/\">B-NDG hCSF1/hTHPO</a> model expresses human colony stimulating factor 1 and thrombopoietin to promote the differentiation and survival of human monocytes and macrophages.Expression of humanized genes on the B-NDG background also permits shaping of the human T cell repertoire in vivo. For example, Biocytogen’s <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hla-a2-1-mice/\">B-NDG HLA-A2.1</a> model (which also includes hβ2M) not only facilitates enhanced differentiation of human CD8+ T cells, but also enables recognition of HLA-restricted epitopes.Another category of next-generation B-NDG models are those adding a targeted murine gene knock-out or mutation. <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-b2m-ko-mice-plus-2/\">B-NDG β2M KO Plus</a> mice lack cell surface expression of MHC-I on dendritic cells. Consequently, engrafted CD8+ T cells cannot mount MHC-I specific T cell responses, extending survival and reducing graft-versus-host responses. This tolerance profile makes it possible to evaluate long-term antitumor effects of therapeutic interventions and/or memory responses in tumor xenograft models bearing reconstituted human immune systems.Biocytogen also offers B-NDG mice which combine both murine gene knock-out and humanized gene expression. This category is exemplified by our <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-b2m-ko-plus-hil15-mice/\">B-NDG β2M KO Plus/hIL-15</a> mice, which were engineered support human NK cell proliferation and expansion in the absence of murine MHC-I or CD8+ T cells. By selective humanization and targeted knockout of genes on the B-NDG background, many dimensions of human immunobiology can be recapitulated and studied in one high-quality model.<h5>Biocytogen: Your Trusted Source for Immunodeficient Mice</h5>Biocytogen’s <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">B-NDG family</a> of highly-immunodeficient mice constitute a suite of powerful tools to answer research questions that remain intractable in standard models. Currently, 23 of our 30 strains of genetically engineered, highly-immunodeficient mouse models are on the B-NDG background. All animals are bred and shipped from our our 540,000 ft2 SPF facility in Haimen, China. Health reports, including screening for over 80 pathogens, are shared prior to shipment transit, which usually takes 1-2 weeks for most destinations.To view a complete listing of currently available models in the B-NDG family, please click <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">here</a>.Related blog: <a href=\"https://biocytogen.com/research-spo...ort-mechanism-driving-t-cell-leukemogenesis/\">Research Impact: B-NDG Mice Used to Identify Lipid Transport Mechanism Driving T Cell Leukemogenesis</a>',1,'/development-history-of-immunodeficient-mice-and-their-research-applications',0,280,1666709667,3796,'us,jp,kr',1666709667,0),(11,'2023 Popular Mouse Models and Cell Lines','Animal Models','','','Our advanced genome editing technologies have been leveraged by our own development scientists to create hundreds of animal and cell models used in biomedical research all over the world.13 years since our founding, Biocytogen’s catalog of off-the-shelf gene-edited animal models, BioMice, now contains more than 450 strains. From <a href=\"https://biocytogen.com/products/ko-mouse-models/\">knock-outs</a> to <a href=\"https://biocytogen.com/animal-cell-models/\">humanized knock-ins</a>, our models are ideal for preclinical evaluation of targeted therapeutics.If you’re looking for models to accelerate antibody discovery, our fully-human antibody mice, <a target=\"_blank\" rel=\"noopener\" class=\"external\" href=\"https://renmab.com/\">RenMice</a>, can spare critical months and costs. Our highly <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">immunodeficient</a> NDG model and its derivatives are superior for engraftment of human immune cells.Check out our most popular model and <a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/\">tumor cell Lines</a> list below! <table cellspacing=\"0\" style=\"border-collapse:collapse; height:722px; width:100%\"><tbody><tr><td colspan=\"2\" style=\"height:66px; text-align:center; width:85.7305%\"> Humanized Immune-Checkpoint Mice </td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\">Name</td><td style=\"height:26px; text-align:center; width:65.443%\">Publications & Resources</td></tr><tr><td style=\"height:107px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf94-1bb-mice/\">B-h4-1BB mice</a></td><td style=\"height:107px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...entiated-cd8-tumor-infiltrating-lymphocytes/\">B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes</a> <a href=\"https://biocytogen.com/publications...by-a-synthetic-tumor-targeted-cd137-agonist/\">Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist</a></td></tr><tr><td style=\"height:45px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3e-mice/\">B-hCD3E mice</a></td><td style=\"height:45px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...ion-of-cd3e-humanized-mice-in-immunotherapy/\">The establishment and application of CD3E humanized mice in immunotherapy</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3edg-mice/\">B-hCD3EDG mice</a></td><td style=\"height:26px; width:65.443%\">Webinar: <a href=\"https://biocytogen.com/webinar/advancing-t-cell-therapies-using-b-hcd3-mouse-models/\">Advancing T cell Therapies Using B-hCD3 Mouse Models</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd40-mice/\">B-hCD40 mice</a></td><td style=\"height:26px; width:65.443%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd40-mice/\">Data package</a></td></tr><tr><td style=\"height:109px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-tghlilrb1-hlilrb4-mice/\">B-Tg(hLILRB1-hLILRB4) mice</a></td><td style=\"height:109px; width:65.443%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-tghlilrb1-hlilrb4-mice/\">Data package</a></td></tr><tr><td style=\"height:10px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-mice/\">B-hPD-1 mice</a></td><td style=\"height:10px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...med-cell-death-ligand-1-anti-pd-1-pd-l1-imm/\">Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy</a> <a href=\"https://biocytogen.com/publications...issociated-rate-and-complete-pd-l1-blockage/\">Tislelizumab uniquely binds to the CC’ loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage</a></td></tr><tr><td style=\"height:51px; text-align:center; width:20.2875%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-pd-l1-mice/\">B-hPD-1/hPD-L1 mice</a></td><td style=\"height:51px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...nternalization-of-programmed-death-ligand-1/\">Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1</a></td></tr><tr><td style=\"height:51px; text-align:center; width:20.2875%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-h4-1bb-mice/\">B-hPD-1/hPD-L1/h4-1BB mice</a></td><td style=\"height:51px; width:65.443%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-h4-1bb-mice/\">Data package</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpvrig-mice/\">B-hPVRIG mice</a></td><td style=\"height:26px; width:65.443%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...l-for-evaluating-anti-pvrig-immunotherapies/\">Humanized PVRIG Mice: A Novel Tool for Evaluating Anti-PVRIG Immunotherapies</a></td></tr><tr><td style=\"height:51px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hsirpa-hcd47-mice/\">B-hSIRPA/hCD47 mice</a></td><td style=\"height:51px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...highly-specific-chimeric-anti-cd47-antibody/\">Preclinical efficacy and toxicity studies of a highly specific chimeric anti-CD47 antibody</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htigit-mice/\">B-hTIGIT mice</a></td><td style=\"height:26px; width:65.443%\">Publications: <a href=\"https://biocytogen.com/publications...iciting-nk-cell-mediated-antitumor-immunity/\">A novel human anti-TIGIT monoclonal antibody with excellent function in eliciting NK cell-mediated antitumor immunity.</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.2875%\"> </td><td style=\"height:24px; width:65.443%\"> </td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hvsig4-mice/\">B-hVSIG4 mice</a></td><td style=\"height:26px; width:65.443%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...vsig4-antibodies-in-humanized-b-hvsig4-mice/\">Evaluating In Vivo Efficacy of Anti-VSIG4 Antibodies in Humanized B-hVSIG4 Mice </a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf4ox40-mice/\">B-hOX40 mice</a></td><td style=\"height:26px; width:65.443%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf4ox40-mice/\">Data package</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.2875%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd16a-mice/\">B-hCD16A mice</a></td><td style=\"height:26px; width:65.443%\"><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd16a-mice/\">Data package</a></td></tr></tbody></table> <table cellspacing=\"0\" style=\"border-collapse:collapse; height:267px; width:100%\"><tbody><tr><td colspan=\"2\" style=\"height:66px; text-align:center; width:85.7305%\"> Immunodeficient Mice </td></tr><tr><td style=\"height:48px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-mice/\">B-NDG Mice</a></td><td style=\"height:48px; width:65.5852%\">Publications: <a href=\"https://biocytogen.com/publications...ssociated-macrophages-pro-myeloma-functions/\">BMI1 regulates multiple myeloma-associated macrophage’s pro-myeloma functions</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-b2m-ko-mice-plus-2/\">B-NDG B2m KO mice plus</a></td><td style=\"height:24px; width:65.5852%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...vl-immune-profiling-after-hpbmc-engraftment/\">Novel Engineered B-NDG B2M KO Mice Plus Shows Delayed GvHD response and Favorable GvL Immune Profiling After hPBMC Engraftment</a></td></tr><tr><td style=\"height:26px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hil15-mice/\">B-NDG hIL15 mice</a></td><td style=\"height:26px; width:65.5852%\">Poster: <a href=\"https://biocytogen.com/posters/io-s...nt-after-human-pbmc-or-cd34-hsc-engraftment/\">B-NDG hIL-15 Mice Improve NK Cell Development After Human PBMC or CD34+ HSC Engraftment</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hthpo-mice/\">B-NDG hTHPO mice</a> </td><td style=\"height:24px; width:65.5852%\"><a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hthpo-mice/\">Data package</a></td></tr></tbody></table> <table cellspacing=\"0\" style=\"border-collapse:collapse; width:100%\"><tbody><tr><td colspan=\"2\" style=\"text-align:center; width:85.7305%\"> Humanized Cytokine Mice </td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2ra-mice/\">B-hIL2RA mice</a></td><td style=\"height:24px; width:65.5852%\">Publications: <a href=\"https://biocytogen.com/publications...ted-to-their-affinity-and-in-vitro-activity/\">Two novel human anti-CD25 antibodies with antitumor activity inversely related to their affinity and in vitro activity</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil36r-mice/\">B-hIL36R mice</a></td><td style=\"height:24px; width:65.5852%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...uation-of-therapeutic-drugs-targeting-il36r/\">Humanized IL36R Mice Provide a Preclinical Tool for the Evaluation of Therapeutic Drugs Targeting IL36R</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil4-il4ra-mice/\">B-hIL4/hIL4RA mice</a></td><td style=\"height:24px; width:65.5852%\">Publications: <a href=\"https://biocytogen.com/publications...del-by-gene-editing-and-efficacy-evaluation/\">The establishment of humanized IL-4/IL-4RA mouse model by gene editing and efficacy evaluation</a></td></tr><tr><td style=\"height:72px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil6-hil6r-mice/\">B-hIL6/hIL6R mice</a></td><td style=\"height:72px; width:65.5852%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...idates-targeting-human-il6-and-il6-receptor/\">Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting human IL6 and IL6 receptor </a></td></tr></tbody></table> <table cellspacing=\"0\" style=\"border-collapse:collapse; width:100%\"><tbody><tr><td colspan=\"2\" style=\"text-align:center; width:100%\"> Humanized GPCR Mice </td></tr><tr><td style=\"text-align:center; width:23.5967%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hglp1r-mice/\">B-hGLP1R mice</a> </td><td style=\"width:76.4033%\"><a href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hglp1r-mice/\">Data package</a></td></tr><tr><td style=\"height:77px; text-align:center; width:23.5967%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hccr8-mice/\">B-hCCR8 mice</a></td><td style=\"height:77px; width:76.4033%\">Poster: <a href=\"https://biocytogen.com/posters/aacr...r-anti-human-ccr8-antibody-drug-development/\">Humanized CCR8 Mouse Model Provides A Translational Tool For Anti-Human CCR8 Antibody Drug Development</a></td></tr></tbody></table> <table cellspacing=\"0\" style=\"border-collapse:collapse; height:166px; width:100%\"><tbody><tr><td colspan=\"2\" style=\"height:66px; width:85.7305%\"> Other Humanized Models </td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hcd38-mice/\">B-hCD38 mice</a></td><td style=\"height:24px; width:65.5852%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hcd38-mice/\">Data package</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/other-humanized-model/b-hfcrn-mice/\">B-hFcRn mice</a></td><td style=\"height:24px; width:65.5852%\">Publications: <a href=\"https://biocytogen.com/publications...cy-in-il-23-induced-psoriasiform-dermatitis/\">IBI112, a selective anti-IL23p19 monoclonal antibody, displays high efficacy in IL-23-induced psoriasiform dermatitis. Int. Immunopharmacol</a> <a href=\"https://biocytogen.com/publications...ces-antibody-directed-phagocytic-activities/\">A single-valent long-acting human CD47 antagonist enhances antibody directed phagocytic activities. Cancer Immunol. Immunother</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hher2-mice/\">B-hHER2 mice</a></td><td style=\"height:24px; width:65.5852%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hher2-mice/\">Data package</a></td></tr><tr><td style=\"height:24px; text-align:center; width:20.1453%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hpsma-mice/\">B-hPSMA mice</a></td><td style=\"height:24px; width:65.5852%\"><a href=\"https://biocytogen.com/products/other-humanized-model/b-hpsma-mice/\">Data package</a></td></tr></tbody></table> <table cellspacing=\"0\" style=\"border-collapse:collapse; height:162px; width:64.9582%\"><tbody><tr><td colspan=\"2\" style=\"height:66px; width:64.9596%\"> Tumor Cell Lines </td></tr><tr><td style=\"height:24px; text-align:center; width:32.9875%\"><a style=\"color: [HASH=44220]#02b9ad[/HASH];\" href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hcd73-mc38/\">B-hCD73 MC38</a></td><td style=\"height:24px; text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hcd73-mc38/\">Data package</a></td></tr><tr><td style=\"height:24px; text-align:center; width:32.9875%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hher2-mc38/\">B-hHER2 MC38</a></td><td style=\"height:24px; text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hher2-mc38/\">Data package</a></td></tr><tr><td style=\"height:24px; text-align:center; width:32.9875%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hcd47-mc38/\">B-hCD47 MC38</a></td><td style=\"height:24px; text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hcd47-mc38/\">Data package</a></td></tr><tr><td style=\"height:24px; text-align:center; width:32.9875%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-htrop2-mc38-plus/\">B-hTROP2 MC38 plus</a></td><td style=\"height:24px; text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-htrop2-mc38-plus/\">Data package</a></td></tr><tr><td style=\"text-align:center; width:32.9875%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hpd-l1-mc38-plus/\">B-hPD-L1 MC38 plus</a></td><td style=\"text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/cell-gene-editing/b-cag-hpd-l1-mc38-plus/\">Data package</a></td></tr><tr><td style=\"text-align:center; width:32.9875%\"><a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/b-hpsma-mc38/\">B-hPSMA MC38</a></td><td style=\"text-align:center; width:31.9721%\"><a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/b-hpsma-mc38/\">Data package</a></td></tr></tbody></table> ',1,'/2023-popular-mouse-models-and-cell-lines',0,1260,1680024919,1064,'us,jp,kr',1680024919,0),(12,'Humanized PCSK9 mice as a resource for lipid management studies','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/1234567-1.png',' Introduction: mitigating dyslipidemia to prevent cardiovascular disease Dyslipidemia is a metabolic derangement that clinically presents with abnormal levels of lipids (cholesterol, triglycerides, and/or phospholipids) in the blood. Specifically, the condition is marked by high levels of low-density lipoprotein (LDL) and low levels of high-density lipoprotein (HDL) cholesterol. Of note, high levels of LDL cholesterol are a major risk factor for cardiovascular disease, due to its ability to accumulate in the walls of arteries, leading to plaque formation and atherosclerosis. Genetic predisposition, as well as poor diet, lack of exercise, obesity, and certain medical conditions can cause dyslipidemia. Early detection and management of dyslipidemia, such as lifestyle modifications and statins, are important for preventing the development and progression of cardiovascular disease. PCSK9: a key target that prevents the removal of LDL from circulation In recent years, an emerging target in the field of lipid-lowering drug development is PCSK9, due to its ability to regulate lipid metabolism in vivo and subsequently affect the occurrence and development of cardiovascular disease. Under physiological conditions, LDL is internalized via clathrin-mediated endocytosis after binding to the LDL receptor (LDLR) on the cell surface of hepatocytes1. Following LDL dissociation from LDLR, due to the acidic environment of the early endosome, LDL particles are subsequently trafficked to the lysosome for degradation1. While a majority of LDLR is recycled back to the plasma membrane, mechanistic studies have revealed two independent routes of PCSK9-induced lysosomal-mediated LDLR degradation1,2. Either intracellular LDLR can be directed from the trans-Golgi to lysosomes for degradation after binding to nascent PCSK9, or secreted PCSK9 binds LDLR at the cell surface, is internalized, which then prohibits endocytic recycling of LDLR, ultimately leading to lysosomal degradation of PCSK9 and LDLR2. Collectively, these studies have shown that PCSK9 blocks the removal of LDL from circulation via LDLR degradation. Following the discovery of PCSK9’s role in LDL metabolism, intense therapeutic interest has focused on identifying modulators capable of inhibiting PCSK9 function in order to reduce LDL levels and prevent subsequent major cardiovascular events. Currently, three FDA-approved pharmaceutical products targeting PCSK9 are available: alirocumab and evolocumab, which are fully humanized monoclonal antibodies, and inclisiran, which blocks intracellular synthesis of PCSK9 via small interfering RNA3. To advance PCSK9 research and drug development, BioMice has independently developed a humanized B-hPCSK9 mouse model, which provides a robust preclinical model for in vivo efficacy evaluation of novel anti-human PCSK9 drugs.  <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hpcsk9-mice/\">B-hPCSK9 mice</a>: a humanized model for testing human PCSK9 therapeutics Model information<table><tbody><tr><td>Strain Name</td><td><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hpcsk9-mice/\">C57BL/6-Pcsk9tm1(PCSK9)/Bcgen</a></td></tr><tr><td>Common Name</td><td><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hpcsk9-mice/\">B-hPCSK9 mice</a></td></tr><tr><td>Background</td><td>C57BL/6 </td></tr><tr><td>Catalog Number</td><td>110928</td></tr><tr><td>NCBI Gene ID</td><td><a href=\"https://www.ncbi.nlm.nih.gov/gene/255738\">255738</a></td></tr><tr><td>Related Genes</td><td>proprotein convertase subtilisin/kexin type 9, FH3, FHCL3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9</td></tr></tbody></table> PCSK9 expression analysis in humanized B-hPCSK9 miceSpecies-specific PCSK9 protein expression analysis in wild-type and humanized B-hPCSK9 mice. Sera was collected from wild-type C57BL/6 (+/+) and homozygous B-hPCSK9 (H/H) mice and analyzed using species-specific PCSK9 ELISA kits. Murine PCSK9 protein was detected in wild-type mice, while human PCSK9 protein was detected in B-hPCSK9 mice.   Analysis of basal lipid metabolism in humanized PCSK9 mice <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/2345678.png\" style=\"height:399px; width:346px\" class=\"aligncenter wp-image-38316\" />Lipid metabolism analysis in wild-type and humanized B-hPCSK9 mice. Plasma concentrations of TG, TC, LDL-C, and HDL-C in wild-type C57BL/6 and humanized B-hPCSK9 mice (n = 36, 6 weeks) were analyzed by Hitachi automatic biochemical analyzer 3110. Levels were similar between wild-type and B-hPCSK9 mice. TG: triglycerides; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.  In vivo efficacy of anti-human PCSK9 antibodies in western diet-induced B-hPCSK9 mice <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/99999-3.png\" style=\"height:398px; width:595px\" class=\"aligncenter wp-image-38319\" />Anti-human PCSK9 antibodies improved lipid metabolism in western diet-induced B-hPCSK9 mice. (A) Humanized B-hPCSK9 mice fed a western-diet, consisting of 40% fat 43% carbohydrates and 1.5% cholesterol, were treated with either alirocumab (internal), evolocumab (internal) or an isotype control antibody (single dose, s.c.) (n=8, male mice).  Blood was collected on days -5, 1, 3, 5 and 8 and analyzed by Hitachi automatic biochemical analyzer 3110. WD-induced B-hPCSK9 mice treated with alirocumab or evolocumab showed reduced (B) LDL-C and (B) TC levels compared to mice treated with an isotype control, indicating that anti-human PCSK9 antibodies were effective in lowering lipid levels in B-hPCSK9 male mice. Values are expressed as averages ± SEMs. TC: total cholesterol; LDL-C: LDL cholesterol; WD: Western diet.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/88888-3.png\" style=\"height:302px; width:351px\" class=\"aligncenter wp-image-38320\" />Anti-human PCSK9 antibodies increased LDLR levels of western diet-induced B-hPCSK9 mice. Humanized B-hPCSK9 mice fed a western-diet were treated with either alirocumab (internal), evolocumab (internal) or an isotype control antibody (single dose, s.c.) (n=6, male mice). Liver tissue was collected on day 8 for ELISA analysis. LDLR levels increased in WD-induced B-hPCSK9 mice treated with anti-human PCSK9 antibodies compared to the isotype control group. Values are expressed as averages ±SEM. LDLR: LDL-cholesterol receptor; WD: Western diet.Explore our <a href=\"https://biocytogen.com/efficacy-toxicity/metabolic-disease-modeling/nash-mouse-models/gan-model/\">Gubra-Amylin diet-induced NASH model</a>! References:1Islam, M. M., Hlushchenko, I., and Pfisterer, S. G. (2022). Low-Density Lipoprotein Internalization, Degradation and Receptor Recycling Along Membrane Contact Sites. Front. Cell Dev. Biol. 10 (826379). doi:10.3389/fcell.2022.8263792Lagace, T. A. (2014). PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells. Curr. Opin. Lipidol. 25 (5), 387-393. Doi:10.1097/MOL.00000000000001143Pokhrel, B., Yuet, W. C., and Levine, S. N. (2022). PCSK9 Inhibitors. In StatPearls. StatPearls Publishing.',1,'/humanized-pcsk9-mice-as-a-resource-for-lipid-management-studies',0,1330,1682350449,1614,'us,jp,kr',1682350449,0),(13,'Immune system-reconstituted models for immuno-oncology research: Applications of CD34+ humanized B-NDG mice','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/001122.png','Introduction:Choosing the right humanized model for your studyThe relative success of immuno-oncology drugs has directed research toward discovering novel targets and therapeutic agents. This has also resulted in heightened demands for the establishment and utilization of relevant, robust animal models for in vivo evaluation of novel preclinical drug candidates. With the shift toward multitargeted antibody-based therapeutics, humanization of important drug target genes, or in some cases, the entire immune system, are strategies that researchers rely on to test whether candidates may be of therapeutic value. Choosing an appropriate humanized model depends on the antigen, target cell type, mechanisms of action, and the modality of therapeutic to be tested. Here, we will provide a brief overview of the types of humanized models available, with a focus on human immune system-reconstituted mice. Types of Humanized ModelsSyngeneic mouse tumor models refers to a murine tumor cell line that can be implanted into immunocompetent mice. Biocytogen’s target humanized mice and/or tumor cell lines are genetically engineered to express human targets of interest in such a way that does not alter intracellular signaling or expression, and the genes remain under control of the respective mouse promoter. This system can be ideal for testing anti-tumor efficacy of antibodies that target human tumor antigens or immune system checkpoints that might not otherwise effectively recognize the murine target.Although some humanized receptors can still recognize murine ligands or co-receptors, in some cases, it may be necessary to genetically humanize the entire signaling complex. Biocytogen’s humanized cytokine/cytokine receptor mice are often engineered to humanize complexes to ensure proper functionality. Read more about Biocytogen’s syngeneic tumor models <a href=\"https://biocytogen.com/humanized-immune-checkpoint-mice-and-syngeneic-mouse-models/\">here</a>.While syngeneic tumor models allow for robust and reproducible efficacy studies, the species differences between human and mouse immune systems remains a significant caveat when interpreting the results. Common animal models, including mouse allograft tumor models, genetically engineered mice, human-derived cell line transplantation models, and human-derived tumor tissue transplantation models, cannot fully recapitulate the human immune system and tumor immune microenvironment, substantially constraining translational research of immune mechanisms and immunotherapy. Consequently, immune reconstitution mouse models that possess a \"humanized\" immune system have emerged as high-quality models in immuno-oncology research and development. These models are often referred to as “HIS models” (humanized immune system models).Types of HIS modelsCurrently, there are three primary categories of mouse models with humanized immune systems. One approach involves reconstructing the human immune system by infusing mature human peripheral blood mononuclear cells (hPBMCs) into immunodeficient mice through either the abdominal cavity or tail vein, known as the hPBMC reconstitution model. Another type involves the injection of human CD34+ hematopoietic stem cells (HSCs) and their progenitors into immunodeficient mice through the abdominal cavity, tail vein, or temporal facial vein of newborns, which also results in the reconstruction of the human immune system, referred to as the HSC (CD34+) reconstitution model. The third type entails transplanting fetal thymus and fetal liver into irradiated severely immunodeficient mice under the renal envelope while simultaneously inoculating human CD34+ hematopoietic stem cells for immune reconstitution, commonly known as the BLT model. This article will focus on the use of Biocytogen’s hCD34+ HSC reconstitution model.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/09876.png\" style=\"height:438px; width:469px\" class=\"aligncenter wp-image-39112\" /> Three ways to humanize immunodeficient mice. Image created using BioRender, based on De La Rochere et al., 2018. Hematopoietic stem cells (HSCs) possess a considerable capacity for self-renewal and diverse differentiation potential, and serve as the precursor to various immune cells. The differentiation of HSCs is reliant on the hematopoietic microenvironment of the bone marrow and thymus, which involves division and proliferation to maintain a relatively constant number, as well as partial proliferation and differentiation into directed progenitors exhibiting surface markers CD34+/CD38+, including lymphoid progenitor cells (CLP) and myeloid progenitor cells (CMP). The CLP further differentiates into T cells, B cells, and NK cells, while the CMP differentiates into monocytes/macrophages, neutrophils, eosinophils, basophils, mast cells, erythrocytes, and platelets. The development of HSCs into mature immune cells at each stage necessitates the involvement of multiple cytokines.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/0099887766.png\" style=\"height:306px; width:462px\" class=\"aligncenter wp-image-39114\" /> Lineage differentiation of hematopoietic stem cells. Image courtesy of BioRender. Establishing a human immune reconstitution model requires a highly immunodeficient mouse recipient. Biocytogen’s severely immunodeficient B-NDG mice, which harbor similar mutations compared with other commercially available immunodeficient mice, completely lack mature T, B, and NK cells. B-NDG mice have been widely published, and are internationally recognized as a valuable tool for human cell or tissue transplantation due to their high degree of lymphoid cell deficiency. Humanization of B-NDG mice therefore involves transplanting human immune cells/ hematopoietic stem cells into B-NDG or B-NDG-derived mice to create immune system-reconstituted mice. Compared to syngeneic models with an intact murine immune system, this approach enables immunological research and evaluation of drugs in the context of a human immune system. The immune reconstitution mouse models can be used to investigate tumor growth in the tumor microenvironment and assess the interplay between tumor cells and immune cells. They are also useful for the study of blood diseases, basic hematopoiesis and immunology, human infectious disease models, as well as drug efficacy evaluation, including immunosuppressants, bispecific antibodies, and ADCC effector function. Using B-NDG mice to establish HSC immune reconstitution modelsSeeding 1.5×105 human CD34+ cells into irradiated B-NDG immunodeficient mice results in HSC differentiation into myeloid and lymphoid lineages, thus establishing the donor’s innate immune system and lymphocytes. Compared with PBMC reconstitution models, the CD34+ immune reconstitution model has a relatively later occurrence of graft-versus-host disease (GvHD) and a longer survival time due to the lower frequency of T cell differentiation.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/0011222.png\" style=\"height:379px; width:165px\" class=\"aligncenter wp-image-39116\" /> <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/908765.png\" style=\"height:345px; width:826px\" class=\"alignnone wp-image-39118\" />The HSC (CD34+) reconstituted model can be used for several applications investigating the role of human immune cells in the context of immunotherapy. In this example, human CD34+ reconstituted B-NDG mice were intravenously injected with 5×105 Raji-Fluc cells. After 5 days, mice were injected (again i.v.) with human PD-1 antibody. After 2 days, the antibody had a significant inhibitory effect on tumor cell expansion, demonstrating that HSC (CD34+)-reconstituted B-NDG mice are valid models for CDX efficacy testing. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/9988776.png\" style=\"height:333px; width:619px\" class=\"aligncenter wp-image-39120\" />Furthermore, this mouse model can also be used for evaluating the efficacy of bispecific antibodies or immune checkpoint inhibitor (ICI) drugs in combination with other drugs, such as a combination of PD-L1 antibody and CD47 antibody. This experimental system not only confirms the efficacy of human ICI antibodies but also benefits from the use of human cell lines or PDX samples, which results in a humanized immune system tumor microenvironment.However, this reconstitution method does have certain limitations. For instance, the differentiating cells are not exposed to human cytokines, which is somewhat limiting for terminal differentiation of certain lineages. As a solution, researchers have attempted to replace mouse cytokine genes by genetically inserting human cytokine genes. In particular, Biocytogen’s humanized cytokine mice are engineered to express human cytokines in situ, so as not to disrupt the regulation of gene expression in vivo.  HSC-B-NDG hIL15 mice: A robust model for human NK development and CAR-NK evaluationIL15 (interleukin 15) is a pleiotropic cytokine that plays a key role in the development of NK cells, natural killer T Cells (NKT) and memory CD8+ T cells. Biocytogen developed a humanized IL-15 immunodeficient mouse model, B-NDG hIL15, by inserting the coding sequence of the human IL15 gene into the 5\' UTR of the mouse IL15 gene. This modification allows the mice to express human IL15 but not mouse IL15. When human HSCs are transplanted into B-NDG hIL15 mice, whether adult or newborn, the reconstitution rate of human NK cells is significantly higher compared to B-NDG mice. This makes B-NDG hIL15 mice an excellent tool to study the development and function of human NK cells and evaluate the efficacy of antibodies that rely on NK cell function, particularly those with ADCC function.Transplantation of CD34+ HSCs into adult B-NDG hIL15 mice enhances human NK cell reconstitution<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/00000000.png\" style=\"height:354px; width:588px\" class=\"aligncenter wp-image-39121\" />Female 6-week-old B-NDG mice (n=17) and B-NDG hIL15 mice (n=19) were exposed to 1.6 Gy irradiation. Human CD34+ HSCs (1.5E5) were injected through the tail vein. Peripheral blood sampling indicates that the proportion of reconstituted human NK cells in B-NDG hIL15 mice was significantly increased compared with B-NDG mice from 2 weeks to 14 weeks post-reconstitution. Efficacy of anti-human CLDN18.2 antibody in huma nHSC-reconstituted adult B-NDG hIL15 mice with tumors <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/6666666.png\" style=\"height:317px; width:635px\" class=\"aligncenter wp-image-39122\" />5-week-old B-NDG hIL15 mice were irradiated with 1.2 Gy and injected with human HSCs (1.5E5) through the tail vein, and subcutaneously injected 6 weeks later with CLDN18.2 overexpressing human lung cancer B-hCLDN18.2 A549 cells (1E7). Mice were subjected to intraperitoneal injection of anti-human CLDN18.2 antibody (zolbetuximab analog) as indicated. Peripheral blood was sampled weekly to detect the reconstitution level of human NK cells and T cells, and tumor tissue was taken at the end of the experiment to detect infiltrated human NK cells and T Cells. The results demonstrate that the anti-human CLDN18.2 antibody could effectively inhibit the growth of tumors, with a tumor suppression rate of 36.2% compared to mice treated with isotype. Human NK cells and T cells are both detected in peripheral blood and tumor tissue, but the frequency of human T cells is lower than human NK cells. Use of neonatal mice for CD34+ HSC engraftmentFor studies that require the multilineage engraftment of CD34s (rather than PBMC-derived T cell reconstitution), one feasible experimental approach is to engraft HSCs directly into the temporal facial vein of newborn mice. This design is lower cost, because fewer HSCs can be injected, and the engraftment can occur while the mice grow old enough for the experiment. It also involves a lower dose of radiation. The example below demonstrates good survival rates and weight gain of neonatal B-NDG and B-NDG hIL15 mice following engraftment.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/9999999.png\" style=\"height:245px; width:629px\" class=\"aligncenter wp-image-39123\" />Furthermore, relevant lymphoid and myeloid lineages are able to develop in both strains following neonatal mouse transplantation with human CD34+ HSCs, as shown below.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/190101201.png\" style=\"height:269px; width:537px\" class=\"aligncenter wp-image-39124\" /><img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/lllllllll.png\" style=\"height:243px; width:645px\" class=\"aligncenter wp-image-39126\" />Transplantation of human CD34+ HSCs in newborn B-NDG hIL15 mice reconstituted functional human NK cellsB-NDG mice (n=10) and B-NDG hIL15 mice (n=10) were injected with CD34+ HSCs (3E4, into the temporal vein) 24-48h after birth, following 0.9 Gy irradiation. Peripheral blood was taken at different time points to detect the reconstitution level of various types of human immune cells. The results demonstrate that the proportion of reconstituted human NK cells in B-NDG hIL15 mice was significantly increased compared with B-NDG mice. SummaryIn summary, by transplanting human tumor cell lines into human CD34+ immune-reconstituted mice, we can assess the responses of multiple human immune cell compartments, providing an optimal model for investigating human tumor-immune cell interactions and therapeutic testing. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/8888888.png\" style=\"height:253px; width:647px\" class=\"aligncenter wp-image-39127\" />A variety of tumor models have been evaluated using Biocytogen’s B-NDG and B-NDG hIL15 mice with immune system reconstitution, and we currently maintain a large supply of  huHSC-B-NDG hIL15 mice. Browse our other engineered B-NDG mice <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">here</a>. References & further reading:[1] De La Rochere P, et al. Humanized Mice for the Study of Immuno-Oncology. Trends Immunol. 2018 Sep;39(9):748-763.[2] Reya T, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11. [3] Rongvaux A, et al. Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol. 2014 Apr;32(4):364-72. [4] Fehniger, et al. Interleukin 15: biology and relevance to human disease. Blood 97, 14-32. ',1,'/immune-system-reconstituted-models-for-immuno-oncology-research-applications-of-humanized-b-ndg-mice-engrafted-with-cd34-hscs',0,1350,1683314071,2177,'us,jp,kr',1683314071,0),(14,'Breaking New Ground in Alzheimer\'s Treatment: A Deep Dive into Lilly\'s Kisunla™ (Donanemab-azbt) FDA Approval','Industry Insights','Alzheimer,Alzheimer disease model,Alzheimer’s disease,Alzheimer’s Treatment,Donanemab,eli lilly,eli lilly fda,Kisunla,lilly fda,mouse model,research','https://cdn.biocytogen.com/web/backend/upload/article/image/Alzheimer-disease.png','The recent FDA approval of Lilly\'s Kisunla™ (donanemab-azbt) for early symptomatic Alzheimer\'s disease marks a monumental breakthrough in combating this debilitating condition. As we celebrate this achievement, it\'s crucial to explore its implications and highlight how our innovative humanized mouse models contribute to advancing Alzheimer\'s research.Kisunla™ targets the amyloid plaques that accumulate in the brains of Alzheimer\'s patients. By promoting the clearance of these plaques, donanemab-azbt potentially slows cognitive decline, offering new hope to patients and emphasizing the importance of innovative research and development. Understanding Alzheimer\'s DiseaseAlzheimer\'s disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide. Characterized by memory loss, cognitive decline, and behavioral changes, AD is identified by the accumulation of amyloid plaques and tau tangles in the brain, disrupting neuronal function and leading to cell death.The approval of Kisunla™ underscores the progress being made in Alzheimer\'s research, highlighting the importance of targeting amyloid pathology and validating advanced preclinical models in drug development. As researchers explore new treatment avenues, robust models like those provided by Biocytogen become increasingly significant. Biocytogen Alzheimer\'s Disease ModelsBiocytogen is at the forefront of Alzheimer\'s research, providing state-of-the-art humanized mouse models that are crucial for understanding disease mechanisms and evaluating potential therapies. Our models closely mimic human disease pathology, offering researchers valuable tools to study Alzheimer\'s and develop new treatments.Aβ-deposition models based on APP/PS1 mutationsThe APP gene encodes a transmembrane protein that, when cleaved, forms Aβ peptides—a process regulated by the PSEN1 gene. Manipulating APP and/or PSEN1 in mouse models therefore provides essential insights into AD pathology, allowing researchers to study the mechanisms of amyloid plaque formation and their impact on neurodegeneration. 5xFAD Models The 5xFAD models express a total of five AD-linked mutations on the APP and PSEN1 transgenes, leading to the formation of amyloid plaques and very high cerebral Aβ42 levels. These models effectively recapitulate numerous AD-related phenotypes and rapidly develop robust amyloid phenotypes, accompanied by gliosis.<ul><li>B-Tg(5xFAD) mice</li><li>ROSA26 5xFAD KI mice</li></ul>For further details on these models, please <a href=\"https://biocytogen.com/contact-us/\">contact us</a>. APP/PS1 ModelsBiocytogen offers a diverse range of additional APP/PS1 models, each carrying one or more AD-associated mutations on the APP and/or PSEN1 genes.<ul><li>B-App NL-F mice</li><li>B-App NL-G-F mice</li><li>B-App NL-F mice/Psen1*M146L*E120K mice</li><li>B-App NL-F mice/Psen1*P117L mice</li><li>B-App NL-F rats</li></ul>For further details on these models, please <a href=\"https://biocytogen.com/contact-us/\">contact us</a>. Tauopathy models and FTD-linked mutationTau pathology, characterized by the abnormal aggregation of tau protein that forms neurofibrillary tangles and leads to neuronal dysfunction, is another common feature of AD. Tauopathy models, like those provided by Biocytogen, are valuable tools that offer crucial insights into tau’s role in AD and help identify potential therapeutic targets.<ul><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-htau-mice/\">B-hTAU mice</a></li><li>B-hTAU*P301S mice</li></ul><img alt=\"Expression of human TAU protein in homozygous B-hTAU mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-15-140241-1.png\" style=\"height:197px; width:600px\" class=\"aligncenter size-full wp-image-51639\" />Expression of human TAU protein in homozygous <a href=\"https://biocytogen.com/products/other-humanized-model/b-htau-mice/\">B-hTAU mice</a>. APOE and TREM2 modelsAPOE and TREM2 are critical risk genes for Alzheimer\'s disease, impacting the buildup and clearance of amyloid plaques. Biocytogen offers humanized mouse models that enable researchers to study these gene’s functions in detail and develop targeted therapies.<ul><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-hapoe2-mice/\">B-hAPOE2 mice</a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-hapoe3-mice/\">B-hAPOE3 mice</a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-hapoe4-mice/\">B-hAPOE4 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-mice/\">B-hTREM2 mice</a></li></ul> <img alt=\"Strain specific APOE expression in B-hAPOE2 and B-hAPOE3 mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-15-141452-1.png\" style=\"height:352px; width:755px\" class=\"aligncenter wp-image-51640\" />Strain specific APOE expression analysis in homozygous B-hAPOE2 (top) and B-hAPOE3 (bottom) mice. <img alt=\"Strain specific TREM2 expression in B-hTREM2 mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-15-142308-2.png\" style=\"height:436px; width:1240px\" class=\"aligncenter wp-image-51641\" />Strain specific TREM2 expression analysis in homozygous <a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-mice/\">B-hTREM2 mice</a>. Other AD risk gene modelsBiocytogen also offers humanized AD models expressing additional risk factors, such as transmembrane glycoproteins, known to impact the function of the blood-brain-barrier in AD.<ul><li>B-hCD98H/hTAU mice</li><li>B-hTFR1/hTAU mice</li><li>B-hCD98H/hTAU*P301S mice</li><li>B-hTFR1/hTAU*P301S mice</li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-htfr1-mice/\">B-hTREM2/hTFR1 mice</a></li></ul> For further details on these models, please <a href=\"https://biocytogen.com/contact-us/\">contact us</a>.Our humanized mouse models have been instrumental in numerous preclinical studies, accelerating the development of potential Alzheimer\'s therapies. Designed to provide reliable data, our models ensure that preclinical findings can be effectively translated into clinical success. Looking Forward: The Future of Alzheimer\'s TreatmentThe approval of Kisunla™ is a beacon of hope for millions affected by Alzheimer\'s disease, signifying progress towards effective treatments and, ultimately, a cure. At Biocytogen, we support this journey by providing researchers with the tools needed to make groundbreaking discoveries.To learn more about our humanized mouse models and how they can advance your Alzheimer\'s research, please <a href=\"https://biocytogen.com/contact-us/\">request a demo</a> to get in touch with our team.',1,'/alzheimers-disease-treatment-lillys-donanemab',0,2090,1721138898,1150,'us,jp,kr',1721138898,0),(15,'From Target to Therapeutics with Humanized Mouse Models','Animal Models','autoimmune disease,drug target humanized model,drug target humanized mouse,humanized mice,humanized mouse,humanized mouse models,metabolic disorders,neurological disorders,oncology','https://cdn.biocytogen.com/web/backend/upload/article/image/Humanized-mouse-model-2.png','Ever wondered how cutting-edge medical research translates lab findings into real-world treatments? At the forefront of this transformation are humanized mice. These lab partners are engineered to carry human elements such as DNA, cells, and immune systems, among others. By incorporating human biological components, humanized mouse models provide a more accurate simulation of human physiological responses, bridging the gap between lab research and clinical trials. Their crucial role allows researchers to achieve more reliable results, and accelerate the development of life-changing therapies. Why Humanized Mouse Models MatterNearly <a href=\"https://www.nature.com/articles/nrd.2016.136\">90% of drugs</a> that enter phase 1 trials ultimately fail to reach the market. This does not account for the unknown failure rate during the preclinical phase. The difficulty in moving from preclinical results to successful human trials is often referred to as the <a href=\"https://link.springer.com/article/10.1186/s41231-019-0050-7\">\"valley of death\"</a>. Conventional mouse models used in preclinical research often fall short in replicating the complexity of the human body, exacerbating the discrepancies between preclinical and clinical results. There is a critical need for advanced models that can more accurately simulate human conditions before moving on to costly and time-consuming clinical trials. This is where humanized mice come into play. Capable of expressing human proteins, exhibiting human immune responses, and developing human-like disease symptoms, humanized mice provide a more accurate representation of disease progression and treatment effects for preclinical research.Creating humanized mice involves advanced engineering techniques. Traditionally, these mice are used to reconstitute the human immune system by transplanting human immune cells into mice that lack an immune response. This setup allows researchers to explore how the human immune system fights infections, influences disease progression, and reacts to immunotherapy. Biocytogen\'s Humanized Mouse ModelsAt Biocytogen, we aim to bridge the gap between lab findings and clinical studies by offering state-of-art humanized mouse models that go beyond traditional methods. In addition to providing immunodeficient mice for grafting human tissues, we have also developed drug target humanized mouse models by incorporating and replacing mouse genes with human ones. These models allow drug candidates to bind with humanized targets, enabling critical in vivo evaluations of drug efficacy, toxicity, and accurate pharmacokinetics/pharmacodynamics (PK/PD). They also support large-scale breeding and minimize variation among individual mice and experimental batches, ensuring consistency and reliability in preclinical studies. Our innovative models are at the forefront of advancing research and accelerating the development of new treatments. Humanized Mice for Oncology Research Humanized mouse models play crucial roles in oncology. A significant area of application lies in the study of immune checkpoints, which are molecules within the immune system that can either enhance or inhibit immune signals. Tumors often manipulate these checkpoints to shield themselves from attacks by the immune system. Checkpoint therapies therefore have been designed to normalize immune function, either by blocking inhibitory checkpoints or by activating stimulatory ones. Biocytogen has created and validated a series of humanized immune-checkpoint mice, enabling comprehensive in vivo evaluations of immune-checkpoint drug candidates. Biocytogen also provides humanized mice that target additional components such as tumor microenvironment (TME) modulators and tumor-associated antigens (TAA). Expanding our portfolio, we have introduced a series of dual/multi-target humanized mice focusing on key molecules such as PD-1/PD-L1, CD3E, 4-1BB, CD16A, and NKP46. These advanced models offer effective strategies for evaluating potential therapies, including antibody-drug conjugates (ADCs) and bispecific antibody treatments, accelerating the development of innovative cancer therapies.Some example models at Biocytogen include:<ul><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htnfrsf94-1bb-mice/\">B-h4-1BB mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-h4-1bb-mice/\">B-hPD-1/hPD-L1/h4-1BB mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-htnfr2/\">B-hTNFR2 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hpd-l1-htnfr2-mice/\">B-hPD-1/hPD-L1/hTNFR2 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd73-mice/\">B-hCD73 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd39-mice/\">B-hCD39 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hpd-1-hcd39-mice/\">B-hPD-1/hCD39 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hccr8-mice/\">B-hCCR8 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3e-mice/\">B-hCD3E mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd3edg-mice/\">B-hCD3EDG mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd16a-mice/\">B-hCD16A mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-tumor-cell-lines/b-htrop2-mc38-plus/\">B-hTROP2 MC38 plus mice</a></li></ul><img title=\"humanized mice for oncology research, targeting immune checkpoints and TME-related targets\" alt=\"humanized mice for oncology research, targeting immune checkpoints and TME-related targets\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-19-100919.png\" style=\"height:227px; width:586px\" class=\"aligncenter wp-image-51719\" /><img title=\"humanized mice for oncology research, targeting double and multiple candidates.\" alt=\"humanized mice for oncology research, targeting double and multiple candidates.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-19-100929.png\" style=\"height:369px; width:588px\" class=\"aligncenter wp-image-51720\" /><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/\">Biocytogen\'s humanized mice for oncology research, targeting immune checkpoints, TME-related targets, and double or multiple candidates.</a> Humanized Mice for Autoimmune DiseasesAutoimmune and inflammatory diseases present significant challenges and opportunities in new drug development. These conditions, which affect <a href=\"https://nationalstemcellfoundation.org/glossary/autoimmune-disease/\">5–8% of the population</a>, encompass a variety of disorders each with distinct pathological mechanisms. To address these, Biocytogen has developed humanized mouse models specifically for autoimmune diseases such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis. These models focus on targeting relevant biomarkers, facilitating the development and testing of new therapeutic strategies.Examples of our models include:<ul><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil4-il4ra-mice/\">B-hIL4/hIL4RA mice</a>   </li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-htslp-htslpr-mice/\">B-hTSLP/hTSLPR mice</a>  </li><li><a href=\"/products/humanized-cytokines_mice/b-hill7a-hil17f-mice/\">B-hIL17A/hIL17F mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil36r-mice/\">B-hIL36R mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil6-hil6r-mice/\">B-hIL6/hIL6R mice</a></li></ul><img title=\"Humanized mice for autoimmune and inflammatory diseases, such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis.\" alt=\"Humanized mice for autoimmune and inflammatory diseases, such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-19-100857.png\" style=\"height:466px; width:608px\" class=\"aligncenter wp-image-51721\" /><a href=\"https://biocytogen.com/efficacy-toxicity/inflammatory-disease-modeling/\">Biocytogen\'s humanized mice for autoimmune and inflammatory diseases, such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis.</a> Humanized Mice for Metabolic DisordersMetabolic disorders significantly impact human health, leading to chronic conditions such as diabetes and obesity. Driven by complex metabolic mechanisms that are not fully understood, these diseases are a major focus of medical research. Recognizing the critical need for advanced treatments and interventions to effectively manage these pervasive health issues, Biocytogen offers humanized mouse models targeting sugar and lipid metabolism. These are applicable to diseases such as diabetes, obesity, fatty liver, fibrosis, and arteriosclerosis. These models help researchers understand the complex mechanisms underlying these conditions and develop new treatments.Examples of our metabolic disorder models:<ul><li><a href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hgcgr-mice/\">B-hGCGR mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-gpcr-mice/b-hglp1r-mice/\">B-hGLP1R mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hpcsk9-mice/\">B-hPCSK9 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hgdf15-mice/\">B-hGDF15 mice</a></li></ul><img title=\"humanized mice for metabolic disorders, including diabetes and obesity, nonalcoholic fatty liver disease, and others.\" alt=\"humanized mice for metabolic disorders, including diabetes and obesity, nonalcoholic fatty liver disease, and others.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-19-151800.png\" style=\"height:286px; width:536px\" class=\"aligncenter wp-image-51722\" /><a href=\"https://biocytogen.com/efficacy-toxicity/metabolic-disease-modeling/\">Biocytogen\'s humanized mice for metabolic disorders, targeting diabetes, obesity, nonalcoholic fatty liver disease, and more.</a> Humanized Mice for Neurological DisordersNeurological disorders affect more than <a href=\"https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext\">3 billion people</a> worldwide and include a diverse range of conditions that impact the brain, spinal cord, and peripheral nerves. Notable examples include Alzheimer\'s disease, Parkinson\'s disease, autism spectrum disorders, and amyotrophic lateral sclerosis, among others. These conditions significantly impair cognitive, emotional, and motor functions, underscoring the critical need for intensive research and innovative drug development. By targeting specific biological pathways involved in the pathology of these disorders, Biocytogen has developed state-of-the-art humanized mice specifically engineered to advance research into these neurological conditions.Examples of our models:<ul><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-htau-mice/\">B-hTAU mice </a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-hapoe4-mice/\">B-hAPOE4 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htrem2-mice/\">B-hTREM2 mice</a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-hlrp5-mice/\">B-hLRP5 mice</a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-htfr1-mice/\">B-hTFR1 mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-higf1r-mice/\">B-hIGF1R mice</a></li><li><a href=\"https://biocytogen.com/products/other-humanized-model/b-httrv30m-mice/\">B-hTTR*V30M mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-hcd98hc-mice/\">B-hCD98HC mice</a></li></ul><img alt=\"Example analysis of strain-specific IGF1R expression in homozygous B-hIGF1R mice by flow cytometry.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-07-26-122716-1.png\" style=\"height:363px; width:382px\" class=\"aligncenter wp-image-51796\" />Example analysis of strain-specific IGF1R expression in homozygous B-hIGF1R mice. Brain was collected from wild-type mice (+/+) and homozygous B-hIGF1R mice, and analyzed by flow cytometry with anti-IGF1R antibody. IGF1R was detectable in wild-type mice and homozygous B-hIGF1R mice, as the antibody is crossly reactive with IGF1R in human and mice. Human IGF1R was exclusively detectable in homozygous B-hIGF1R but not in wild-type mice. Embark on a Journey of Discovery with BiocytogenDidn\'t find what you\'re looking for? Beyond the models already mentioned, Biocytogen offers a variety of other humanized mice, including customizable options that allow researchers to tailor the mouse genome to specific research needs. By more closely mimicking human physiological responses, our humanized mice play a crucial role in transitioning from theoretical research to practical, life-saving drug development.<a href=\"https://biocytogen.com/contact-us/\">Contact us</a> today to discover how Biocytogen’s humanized mouse models can advance your research! References<a href=\"https://www.nature.com/articles/nrd.2016.136\">Mullard, Asher.</a> \"Parsing clinical success rates.\" Nature Reviews Drug Discovery 15.7 (2016): 447-448.<a href=\"https://link.springer.com/article/10.1186/s41231-019-0050-7\">Seyhan, Attila A.</a> \"Lost in translation: the valley of death across preclinical and clinical divide–identification of problems and overcoming obstacles.\" Translational Medicine Communications 4.1 (2019): 1-19.<a href=\"https://doi.org/10.3389/fonc.2021.784947\">Cogels, Morgane M., et al.</a> \"Humanized mice as a valuable pre-clinical model for cancer immunotherapy research.\" Frontiers in oncology 11 (2021): 784947.<a href=\"https://retrovirology.biomedcentral.com/articles/10.1186/s12977-021-00557-1\">Dash, Prasanta K., et al.</a> \"Humanized mice for infectious and neurodegenerative disorders.\" Retrovirology 18.1 (2021): 13.<a href=\"https://www.mdpi.com/1999-4923/15/6/1600\">Karnik, Isha, et al.</a> \"Emerging preclinical applications of humanized mouse models in the discovery and validation of novel immunotherapeutics and their mechanisms of action for improved cancer treatment.\" Pharmaceutics 15.6 (2023): 1600.<a href=\"https://nationalstemcellfoundation.org/glossary/autoimmune-disease/\">National Stem Cell Foundation.</a> \"Autoimmune Disease\".<a href=\"https://doi.org/10.1016/S1474-4422(24)00038-3\">Steinmetz, Jaimie D., et al.</a> \"Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021.\" The Lancet Neurology 23.4 (2024): 344-381.',1,'/humanized-mouse-models',0,2100,1722259981,2565,'us,jp,kr',1722259981,0),(16,'Conquering the Inner Struggle: Mastering Autoimmune and Inflammatory Diseases','Animal Models','autoimmune,Autoimmune and Inflammatory Diseases,autoimmune disease,inflammation,inflammatory disease','https://cdn.biocytogen.com/web/back...ge/Autoimmune-and-Inflammatory-Diseases-1.png','It\'s well-known that a robust immune system is fundamental to good health. Yet, did you know that our immune system, designed to protect us, can sometimes turn against us, attacking the body itself? This troubling issue lies at the heart of autoimmune diseases. In these conditions, the immune system mistakenly targets healthy tissues, causing inflammation and damage. With up to <a href=\"https://www.sciencedirect.com/science/article/pii/S0896841109001589\">10%</a> of the world population affected, understanding this unexpected behavior is crucial for developing more effective treatments and improving patient outcomes.Autoimmune diseases come in various forms, including rheumatoid arthritis, psoriasis, multiple sclerosis, lupus, inflammatory bowel disease, Hashimoto’s thyroiditis, and more. These conditions target different areas: rheumatoid arthritis affects joint linings, multiple sclerosis damages nerve cell coatings, and lupus can impact multiple organs like the skin, joints, brain, heart, and lungs. Inflammation is a common feature across these diseases, leading to symptoms like joint pain, rashes, fevers, and fatigue, depending on the affected areas. What are the Triggers?Autoimmune diseases occur when the immune system mistakenly attacks its own tissues or overreacts to normal antigens, affecting various organs and tissues. These conditions can produce symptoms that range from mild to severe. The exact causes are complex and not fully understood, but <a href=\"https://newsinhealth.nih.gov/2022/06/understanding-autoimmune-diseases\">several potential contributors</a> have been identified:<ul><li>Genetic Factors: Autoimmune diseases often run in families, suggesting a genetic link in conditions like rheumatoid arthritis and multiple sclerosis.</li><li>Environmental Triggers: Factors such as viral infections, exposure to toxins like cigarette smoke, and high-salt diets can impair immune function, leading to autoimmune diseases.</li><li>Lifestyle Risks: Smoking, obesity, and diets high in fats and sugars can increase inflammation and alter immune responses, heightening the risk of autoimmune diseases.</li><li>Multiple Autoimmune Syndrome (MAS): Individuals with one autoimmune disease are more likely to develop additional autoimmune disorders.</li></ul> Fighting the ConditionUnderstanding immune system dysregulation in autoimmune and inflammatory diseases is crucial for combating these disorders. Some key factors include:<ul><li>Loss of Self-Tolerance: This occurs when the immune system loses its ability to differentiate between the body’s own cells and foreign invaders, leading to self-attacks.</li><li>Molecular Mimicry: In this phenomenon, pathogens mimic the appearance of the body’s cells, causing the immune system to erroneously attack these cells.</li><li>Epitope Spreading: Over time, the immune response can mistakenly expand to include additional antigens that are related yet distinct from the original targets.</li><li>Cytokine Imbalance: An imbalance in cytokines, which are vital for regulating immune responses, can lead to unchecked inflammation and subsequent tissue damage.</li><li>T Cell and B Cell Dysregulation: Dysfunctional T cells and B cells, crucial components of the immune system, start attacking the body’s tissues, worsening the diseases\' effects.</li></ul>While a cure for autoimmune and inflammatory diseases remains elusive, researchers are actively working to devise strategies that manage symptoms and combat these disorders. Each disease involves unique immune pathways and cellular interactions, requiring a deep understanding of biological mechanisms. This knowledge is crucial for developing targeted therapies that precisely correct the immune system\'s actions without broadly suppressing it. What Biocytogen OffersBiocytogen is at the cutting edge of advancing drug development for autoimmune and inflammatory diseases. We offer humanized mouse models that replace mouse genes with their human counterparts, enabling precise preclinical testing of drugs in a human genetic context. Additionally, we have developed fully human antibodies that target key pathways involved in these diseases, providing efficient solutions for novel therapy development. Humanized Mice for Autoimmune and Inflammatory DiseasesBiocytogen has developed <a href=\"https://biocytogen.com/efficacy-toxicity/inflammatory-disease-modeling/\">humanized mice specifically tailored for autoimmune diseases</a> such as asthma, atopic dermatitis, psoriasis, intestinal inflammation, and rheumatoid arthritis. These models express human candidate genes, enabling drug candidates to interact with human-specific targets. This approach is critical for in vivo evaluations of drug efficacy, toxicity, and pharmacokinetics/pharmacodynamics (PK/PD), accelerating the drug development process and bringing effective treatments to patients more quickly.Examples of our models include:<ul><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil4-il4ra-mice/\">B-hIL4/hIL4RA mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-htslp-htslpr-mice/\">B-hTSLP/hTSLPR mice</a></li><li><a rel=\"noopener\" href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hill7a-hil17f-mice/\">B-hIL17A/hIL17F mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil36r-mice/\">B-hIL36R mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil6-hil6r-mice/\">B-hIL6/hIL6R mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htl1a-mice/\">B-hTL1A mice</a></li><li><a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hige-hfcer1a-mice/\">B-hIgE/hFCER1A mice</a></li></ul><img alt=\"Biocytogen’s humanized mice for autoimmune and inflammatory diseases\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-15-112123.png\" style=\"height:723px; width:1617px\" class=\"aligncenter size-full wp-image-51911\" />Biocytogen’s humanized mice for autoimmune diseases Fully Human Antibodies for Autoimmune and Inflammatory DiseasesBiocytogen has developed over 20 innovative fully human antibodies targeting key pathways in autoimmune and inflammatory diseases using our proprietary <a href=\"https://biocytogen.com/renmice-platforms/\">RenMice®</a> platforms. Notably, our anti-OSM and anti-OSMR monoclonal antibodies target components of the IL-6 cytokine family, which are elevated in chronic inflammatory conditions with fibrosis, and have shown remarkable efficacy compared to existing treatments. These antibodies effectively inhibit OSM and IL-31 functions, making them promising candidates for treating inflammatory skin diseases, pulmonary fibrosis, and inflammatory bowel disease.Biocytogen is advancing asthma therapies by developing fully human antibodies targeting IGHE, which block IgE binding to FCER1A and CD23, inhibiting mast cell and basophil degranulation to reduce inflammation. These antibodies hold promise for treating asthma and other IgE-mediated diseases. Our antibodies against ST2, the IL-33 receptor involved in allergic reactions and chronic inflammation, also offer potential benefits for these conditions. The Path Forward Ongoing research brings renewed hope for breakthroughs and potential cures for autoimmune and inflammatory diseases. As we unravel these complexities, Biocytogen is committed to pioneering innovative treatments and accelerating their transition from lab to clinic. <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> to learn how our cutting-edge products and services can advance your research and explore co-development or licensing opportunities! References<a href=\"https://www.sciencedirect.com/science/article/pii/S0896841109001589\">Shapira, Yinon, Nancy Agmon-Levin, and Yehuda Shoenfeld.</a> \"Defining and analyzing geoepidemiology and human autoimmunity.\" Journal of autoimmunity 34.3 (2010): J168-J177.<a href=\"https://newsinhealth.nih.gov/2022/06/understanding-autoimmune-diseases\">NIH News in Health</a>. “Understanding Autoimmune Diseases”. (2022)<a href=\"https://www.healthline.com/health/autoimmune-disorders\">Healthline</a>. “Everything to Know About Autoimmune Diseases”. (2024)<a href=\"https://www.nature.com/articles/s41581-023-00720-1\">Pisetsky, David S.</a> \"Pathogenesis of autoimmune disease.\" Nature Reviews Nephrology 19.8 (2023): 509-524.',1,'/autoimmune-inflammation-disease-blog',0,2130,1723751005,2343,'us,jp,kr',1723751005,0),(17,'Charting New Frontiers in GvHD Treatment: Insights from Niktimvo™ FDA approval','Industry Insights','axatilimab,FDA,FDA approval,graft-versus-host disease,GvHD,Niktimvo,treatment','https://cdn.biocytogen.com/web/backend/upload/article/image/Blog-cover-GVHD.png','On August 14, 2024, Syndax and Incyte announced the FDA approval of Niktimvo™ (axatilimab-csfr), a CSF-1R monoclonal antibody, for the treatment of chronic graft-versus-host disease (GvHD). Axatilimab is the first CSF-1R monoclonal antibody to receive approval, specifically targeting the drivers of inflammation and fibrosis in chronic GvHD (<a href=\"https://www.businesswire.com/news/home/20240814470216/en/\">Business Wire, 2024</a>). CSF-1R, a cell surface protein, plays a critical role in regulating the survival and function of monocytes and macrophages. Preclinical studies have demonstrated that inhibiting CSF-1R signaling can significantly reduce the population of disease-mediating macrophages and their monocyte precursors. This reduction is crucial for combating the fibrosis seen in chronic GvHD and other potential disorders, such as idiopathic pulmonary fibrosis (IPF). About GvHDFirst reported by <a href=\"https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1962.tb45321.x\">Barnes et al.</a> in 1962 and later defined by <a href=\"https://cir.nii.ac.jp/crid/1571417124328004864\">Billingham (1996)</a>, GvHD is a complex, multi-organ systemic disorder in which donor lymphocytes attack the recipient’s organs during immune reconstitution and hematopoietic recovery following transplantation. Between 30% and 50% of transplant patients develop acute GvHD (aGvHD) post-transplantation. As one of the most common and severe complications of allogeneic hematopoietic stem cell transplantation, GvHD significantly affects patient mortality and post-transplant outcomes. The primary treatment, typically involving corticosteroids and other immunosuppressants, often yields suboptimal results. This highlights the critical need to develop more effective treatment strategies.Mouse models have been instrumental in providing vital insights into the pathophysiological mechanisms of GvHD, thereby improving the success rates of human hematopoietic stem cell transplants (HSCT). These models have revealed significant differences in the pathophysiology of acute and chronic GvHD, enhancing our understanding of the immune responses involved, including antigen processing and presentation, the role of the thymus, and immune reconstitution post-transplant (<a href=\"https://doi.org/10.1242/dmm.006668\">Schroeder et al., 2011</a>).<img alt=\"Stages of Acute and Chronic GvHD in Mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-131138.png\" style=\"height:942px; width:940px\" class=\"aligncenter size-full wp-image-52027\" />Left image: Stages of Acute GvHD in Mice. This diagram illustrates the sequence of events during the development of aGvHD in mice. The five stages include: immune priming (A), activation (B), T-cell expansion (C), T-cell trafficking (D), and host tissue injury (E). (Source: <a href=\"https://doi.org/10.1242/dmm.006668\">Schroeder et al., 2011</a>)Right image: Stages of Chronic GvHD (cGvHD) in Mice. The diagram details the sequence of events during the development of cGvHD in mice. The stages are as follows: immune priming (A), activation of T cells and B cells (B), T cells expansion and B cell autoantibody production (C), trafficking to sited of tissue damage (D), and end organ damage resulting from chronic inflammation and fibrosis (E). (Source: <a href=\"https://doi.org/10.1242/dmm.006668\">Schroeder et al., 2011</a>) GvHD Mouse Models at BiocytogenBiocytogen has developed a range of GvHD mouse models leveraging its proprietary B-NDG immunodeficient mice and humanized mouse models developed based on these B-NDG mice.  Establishment of GvHD mouse models<img alt=\"Establishment of GvHD Mouse Models\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-140505.png\" style=\"height:376px; width:1416px\" class=\"aligncenter size-full wp-image-52039\" />These models are assessed biweekly for symptoms of GvHD including weight loss, posture, activity levels, fur texture, and skin damage, with the most relevant metric being animal survival rates.  Evaluation of GvHD mouse models<img alt=\"Evaluation of GvHD Mouse Models\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133250.png\" style=\"height:395px; width:1593px\" class=\"aligncenter size-full wp-image-52029\" />Survival curves, weight changes and clinical scores in humanized GvHD mouse models created using different human peripheral blood mononuclear cell (hPBMC) donors. Variations in GvHD severity may occur depending on the hPBMC donor used. Prior to selecting PBMC donors for preclinical efficacy testing, it is crucial to pre-characterize these donors by assessing survival rates, weight changes, and clinical GvHD scores. <img alt=\"Preclinical efficacy of OX40 antibodies in B-NDG mice transplanted with human PBMCs. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133307.png\" style=\"height:318px; width:1600px\" class=\"aligncenter size-full wp-image-52030\" />Preclinical efficacy of OX40 antibodies (telazorlimab) in B-NDG mice transplanted with human PBMCs. Studies have shown that OX40 antibodies enhance survival rates compared to control groups. Clinical scoring criteria for GvHD in mouse models<img alt=\"Clinical scoring criteria for GvHD in mouse models\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133325.png\" style=\"height:372px; width:357px\" class=\"aligncenter wp-image-52031\" />Impact of radiation doses and PBMC injection volumes on GvHD model construction<img alt=\"Impact of radiation doses and PBMC injection volumes on GvHD model construction\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133350.png\" style=\"height:785px; width:1112px\" class=\"aligncenter size-full wp-image-52032\" />Effects of different PBMCs and injection volumes on GvHD model development<img alt=\"Effects of different PBMCs and injection volumes on GvHD model development\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133507.png\" style=\"height:827px; width:1227px\" class=\"aligncenter size-full wp-image-52033\" /><img alt=\"Effects of different PBMCs and injection volumes on GvHD model development\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133520.png\" style=\"height:830px; width:1481px\" class=\"aligncenter size-full wp-image-52034\" />Hematoxylin and eosin (H&E) staining in GvHD mouse models<img alt=\"Hematoxylin and eosin (H&E) staining in GvHD mouse models\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-08-29-133603.png\" style=\"height:859px; width:1841px\" class=\"aligncenter size-full wp-image-52035\" />On day 7, G1 mice show no significant pathological changes, while G2 and G3 mice exhibit reductions in splenic lymphocyte counts due to radiation, with substantial monocyte and granulocyte presence in G3 spleens. By day 14, G1 and G2 mice continue to exhibit no significant pathology; however, G3 mice display increased splenic granulocytes/lymphocytes and mixed inflammatory cell infiltration in the liver, lungs, and kidneys. Additionally, scattered patchy necrosis is observed in these organs, along with congestion and bleeding in the duodenum and jejunum, and patchy bleeding and necrosis in the spleen. The FDA\'s approval of Niktimvo™ marks a significant breakthrough in the treatment of chronic GvHD, offering new hope to patients. At Biocytogen, we are committed to supporting this progress by equipping researchers with the tools necessary to further explore and improve GvHD therapies. <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> today to learn more about our products and services! References<a href=\"https://www.businesswire.com/news/home/20240814470216/en.\">Business Wire</a>. Incyte and Syndax Announce U.S. FDA Approval of Niktimvo™ (axatilimab-csfr) for the Treatment of Chronic Graft-Versus-Host Disease (GVHD).<a href=\"https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1962.tb45321.x\">Barnes, D. W. H., J. F. Loutit, and H. S. Micklem.</a> \"“Secondary disease” of radiation chimeras: a syndrome due to lymphoid aplasia.\" Annals of the New York Academy of Sciences 99.3 (1962): 374-385.<a href=\"https://cir.nii.ac.jp/crid/1571417124328004864\">Billingham, Rupert E.</a> \"The biology of graft-versus-host reaction.\" Harvey Lect. 62 (1996): 21-78.<a href=\"https://doi.org/10.1242/dmm.006668\">Schroeder, Mark A., and John F. DiPersio</a>. \"Mouse models of graft-versus-host disease: advances and limitations.\" Disease models & mechanisms 4.3 (2011): 318-333.',1,'/gvhd-treatment-niktimvo-fda-approval',0,2150,1725457855,2353,'us,jp,kr',1725457855,0),(18,'The Blood-Brain Barrier: A Double-Edged Sword in Neurology','Animal Models','BBB,Blood brain barrier,brain drug delivery,CD98HC,Central nervous system,CNS,drug delivery,TFR1','https://cdn.biocytogen.com/web/backend/upload/article/image/Weixin-Image_20240916090821.png','The brain, our most intricate and vital organ, is safeguarded by a unique structure known as the blood-brain barrier (BBB). Acting as a fortress, the BBB keeps harmful substances out while preserving the delicate environment of the brain. This protective mechanism, however, also poses significant challenges in developing drugs for the central nervous system (CNS). With fewer than 5% of evaluated drugs successfully crossing the BBB, this field of pharmaceutical research faces notably high costs and lengthy development cycles (<a href=\"https://link.springer.com/article/10.1007/s40263-020-00766-w\">Haumann et al., 2020</a>).<img alt=\"Blood brain barrier\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-12-120858.png\" style=\"height:452px; width:688px\" class=\"aligncenter wp-image-52277\" /> The BBB as a Bottleneck in CNS Drug DevelopmentMore than one in three people worldwide are affected by neurological disorders, leading to profound suffering for individuals and their families (<a href=\"https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext\">Steinmetz et al., 2024</a>). These conditions have emerged as the leading causes of disability and ill health globally, with the overall impact of disability, illness, and premature death rising by 18% since 1990 (<a href=\"https://www.who.int/news/item/14-03-2024-over-1-in-3-people-affected-by-neurological-conditions--the-leading-cause-of-illness-and-disability-worldwide#:~:text=Neurological conditions are now the,increased by 18% since 1990.\">World Health Organization, 2024</a>). Despite significant research investment, the BBB remains a major bottleneck in developing effective treatments. To overcome this hurdle, considerable work has also gone into devising effective methods for drug delivery across the BBB. Some key areas of ongoing research include:<ul><li>Receptor-Mediated Transport (RMT): This strategy leverages the BBB\'s natural transport mechanisms. Drugs are attached to ligands that bind to specific receptors, such as transferrin or insulin receptors, on the BBB. This interaction triggers receptor-mediated endocytosis, allowing drugs to be transported into the brain within vesicles.</li><li>Nanoparticle-Based Delivery: Nanoparticles are engineered to encapsulate drugs, which are then coated to evade immune detection. These coatings may include ligands that enhance uptake through RMT, improving the delivery process.</li><li>Focused Ultrasound: This method employs ultrasound waves in conjunction with microbubbles to create a temporary disruption in the BBB, allowing drugs to pass through more readily.</li><li>Molecular Trojan Horses: By linking drugs to molecules that naturally cross the BBB, this technique supports RMT by using peptides or other carriers to ferry drugs across the barrier.</li></ul> Animal Models for BBB Research at BiocytogenTo advance the development of more effective drug delivery methods across the BBB, Biocytogen has developed a series of humanized animal models. In these models, key mouse targets involved in natural BBB transport, which also hold potential for delivering therapeutic agents, have been replaced with their human counterparts. This enables in vivo testing of drug delivery mechanisms using humanized candidates, allowing for more accurate evaluations of therapies aimed at crossing the BBB in preclinical studies. Humanized mice of TFR1 (B-hTFR1 mice)<img alt=\"Genetic strategy for humanized mice of TFR1 at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-17-112209.png\" style=\"height:239px; width:345px\" class=\"aligncenter wp-image-52278\" />(Source: <a href=\"https://www.science.org/doi/10.1126/science.adm8386\">Huang et al., 2024</a>) TFR1, predominantly expressed on brain endothelial cells, acts as a crucial gateway for transferrin-bound iron to enter the CNS. It is part of the RMT system and the most widely studied target for CNS drug delivery. Biocytogen has developed humanized TFR1 mice by replacing exons 4-19 of the mouse Tfr1 gene, which encode the extracellular region, with the corresponding human TFR1 exons. A <a href=\"https://www.science.org/doi/10.1126/science.adm8386\">recent study published in Science</a> using our B-hTFR1 mouse model revealed that their optimized AAV, which binds to human TFR1, can not only get into the CNS but also deliver a therapeutically relevant protein that is lacking in Gaucher disease (<a href=\"https://www.science.org/doi/10.1126/science.adm8386\">Huang et al., 2024</a>). Our humanized TFR1 mice enable researchers to more accurately study drug delivery pathways in a human gene context in preclinical studies, accelerating the development of CNS-targeted therapies.<img alt=\"Immunofluorescence staining of brain sections from WT and B-hTFR1 mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-17-123651.png\" style=\"height:454px; width:1218px\" class=\"aligncenter size-full wp-image-52283\" />Immunofluorescence staining of brain sections from WT and B-hTFR1 mice. Nuclei are stained blue, the mouse endothelial cell marker mCD31 is red, and human TFR1 (hTFR1) is green. hTFR1, absent in WT (left), was observed in B-hTFR1 mice (right) and expressed in brain endothelial cells, suggesting a method for drugs to cross the BBB via hTFR1-mediated transendocytosis. <img alt=\"B-hTFR1 mice received intravenous injections of control IgG or anti-human TFR1 BsAbs.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-17-122301.png\" style=\"height:429px; width:1804px\" class=\"aligncenter size-full wp-image-52282\" />B-hTFR1 mice received intravenous injections of control IgG or anti-human TFR1 BsAbs. Brain and serum samples collected at various time points showed quantified antibody concentrations, revealing higher brain exposure and serum clearance for the BsAbs. This suggests the BsAbs can cross the blood-brain barrier in B-hTFR1 mice. Humanized mice of CD98HC (B-hCD98HC mice)CD98HC plays a pivotal role in maintaining the integrity of the BBB and in nutrient transport, including amino acid transport, integrin signaling, and cellular stress responses. Given its critical functions, CD98HC is being explored as a potential target for drug delivery to the brain, opening new avenues for treating CNS disorders. Biocytogen has developed humanized mice of CD98HC to support related research. <img alt=\"Strain-specific CD98 expression in mouse brains was analyzed using immunofluorescence staining. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-17-131335.png\" style=\"height:604px; width:1640px\" class=\"aligncenter size-full wp-image-52295\" />Strain-specific CD98 expression in mouse brains was analyzed using immunofluorescence staining. Brain sections from WT (left) and homozygous B-hCD98HC (right) mice were stained with anti-human CD98HC (green) and anti-mouse CD31 antibodies (red). Human CD98 was exclusive to the microvascular endothelium of B-hCD98HC mice, absent in WT mice. Customizable Models and Pharmacological ServicesIn addition to our standard models, Biocytogen offers customizable options to develop mouse models tailored to meet your specific research needs. We also provide comprehensive pharmacological services, which include in vitro and in vivo evaluations of drug efficacy, toxicity, and precise pharmacokinetics/pharmacodynamics (PK/PD) profiling. Contact us to learn how our products and services can enhance your research involving the BBB!Animal Models for BBB Research at Biocytogen<img alt=\"Animal Models for BBB Research at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-24-112239.png\" style=\"height:784px; width:1034px\" class=\"aligncenter size-full wp-image-52404\" />Webinar on NeuroscienceJoin Dr. Dong Han, Sr. Scientist and Neurological Disease Team Lead at Biocytogen, for a webinar on Oct 2 at 1 PM EST, 2024. Explore the fundamentals of neurological disorders and the crucial role of animal models in revealing disease mechanisms and evaluating therapies. We\'ll also highlight Biocytogen’s specialized animal models and innovations for neurological conditions and BBB transport. Don’t miss this opportunity to learn how these advanced tools are transforming studies of neurological diseases, providing new insights, and advancing therapeutic approaches!<a href=\"https://biocytogen.com/webinar/advances-in-neurological-disease-animal-models/\">Click here </a>to request access to the on-demand video!<a href=\"https://biocytogen.zoom.us/webinar/register/WN_vJqZVLd0Q-GZdJBYb_PiDA#/registration\"><img alt=\"Biocytogen Webinar Series- Advances in Neurological Disease Animal Models\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Webinar-template-Dong-1-1.png\" style=\"height:1080px; width:1920px\" class=\"aligncenter size-full wp-image-52286\" /></a> References<a href=\"https://link.springer.com/article/10.1007/s40263-020-00766-w\">Haumann, Rianne, et al.</a> \"Overview of current drug delivery methods across the blood–brain barrier for the treatment of primary brain tumors.\" CNS drugs 34.11 (2020): 1121-1131.<a href=\"https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext\">Steinmetz, Jaimie D., et al.</a> \"Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021.\" The Lancet Neurology 23.4 (2024): 344-381.<a href=\"https://www.who.int/news/item/14-03-2024-over-1-in-3-people-affected-by-neurological-conditions--the-leading-cause-of-illness-and-disability-worldwide#:~:text=Neurological conditions are now the,increased by 18% since 1990.\">World Health Organization</a>. “Over 1 in 3 people affected by neurological conditions, the leading cause of illness and disability worldwide.” (2024)<a href=\"https://www.science.org/doi/10.1126/science.adm8386\">Huang, Qin, et al.</a> \"An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery.\" Science 384.6701 (2024): 1220-1227.',1,'/blood-brain-barrier-drug-delivery-tfr1-cd98hc',0,2170,1726597970,3983,'us,jp,kr',1726597970,0),(19,'Unlocking the Autism Puzzle: Genes, Minds, and Untold Possibilities','Animal Models','ASD,autism,autism spectrum disorder,mouse model,neuroscience','https://cdn.biocytogen.com/web/backend/upload/article/image/2024-Autism-Spectrum-Disorder.png','Autism Spectrum Disorder (ASD), often identified in early childhood, presents challenges in social interactions, communication, and repetitive behaviors. The term \"spectrum\" reflects the wide range of abilities, with some individuals displaying exceptional skills, while others face significant difficulties, such as non-verbal communication, aggression, epilepsy, and self-injury. Sometimes referred to as \"children of the stars,\" individuals with ASD may possess remarkable talents, with about a third showing superior abilities in one or more areas (<a href=\"https://doi.org/10.1098/rstb.2008.0328\">Howlin et al., 2009</a>).The prevalence of ASD has been rising, now affecting approximately 1 in 36 children in the U.S., according to the CDC (<a href=\"https://www.cdc.gov/mmwr/volumes/72/ss/ss7202a1.htm\">Maenner et al., 2023</a>). Understanding ASD is vital for promoting inclusion and support, both for those diagnosed and the broader community. What Causes ASD?While progress has been made in understanding ASD, its exact causes remain unclear. Both environmental and genetic factors play a role. Environmental risks include parental age, maternal health, and pregnancy complications (<a href=\"https://journals.lww.com/jrms/fullt...ntal_factors_influencing_the_risk_of.27.aspx\">Karimi et al., 2017</a>). However, genetics is a key contributor, with heritability estimated at 90% (<a href=\"https://www.tandfonline.com/doi/full/10.3109/1547691X.2010.545086\">Ratajczak, 2011</a>). Research has identified hundreds of genetic variations linked to ASD (<a href=\"https://gene.sfari.org/\">SFARI gene</a>). Some cases of autism can be directly traced to specific genetic disorders like Rett syndrome (MECP2) and Fragile X syndrome (FMR1). In other cases, genetic mutations may elevate the risk of developing ASD. Advancing Autism Research with Genetically Modified ModelsAt Biocytogen, we’re committed to advancing the understanding of ASD by developing genetically modified animal models that mirror the genetic variations seen in individuals with ASD. By targeting key genes like MECP2 and FMR1, our models provide crucial insights into how these genetic changes contribute to the development of autism. B-MeCP2 KO MiceMECP2 (Methyl-CpG-binding protein 2), located on the X chromosome, is crucial for brain development and function. Loss of MECP2 disrupts synaptic processes and neuronal signaling, causing cognitive, motor, and behavioral symptoms linked to ASD. To advance research into MECP2-related autism, Biocytogen has developed Mecp2 knockout mouse models that closely mimic the genetic background of human MECP2-related ASD, providing researchers with a valuable tool for studying disease mechanisms and exploring potential therapies. <img alt=\"MECP2 is absent in B-MeCP2 KO mice. Tissue lysates were prepared from wild-type (+/+) and B-MeCP2 KO (Δ/Y) mice for analysis.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-30-162050.png\" style=\"height:229px; width:848px\" class=\"wp-image-52481\" /> MECP2 is absent in <a href=\"https://biocytogen.com/products/induced-disease-model-mice/b-mecp2-ko-mice/\">B-MeCP2 KO mice</a>. Tissue lysates were prepared from wild-type (+/+) and B-MeCP2 KO (Δ/Y) mice for analysis. B-Fmr1 KO miceThe FMR1 (Fragile X Mental Retardation 1) gene plays a crucial role in regulating synaptic function and neural plasticity, which are essential for proper brain development. Mutations or silencing of the FMR1 gene lead to Fragile X Syndrome (FXS), the most common inherited form of intellectual disability and a significant genetic contributor to ASD. This makes FMR1 a key focus in studying the molecular mechanisms of ASD and developing targeted treatments. To support research into FXS, Biocytogen has developed Fmr1 KO mice that mimic the human genetic background.<img alt=\"FMRP protein is absent in homozygous B-Fmr1 KO mice. Tissue lysates were prepared from wild-type (+/+) and B-Fmr1 KO (-/-) mice for analysis.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-30-161702.png\" style=\"height:198px; width:772px\" class=\"wp-image-52480\" /> FMRP protein is absent in homozygous <a href=\"https://biocytogen.com/products/induced-disease-model-mice/b-fmr1-ko-mice/\">B-Fmr1 KO mice</a>. Tissue lysates were prepared from wild-type (+/+) and B-Fmr1 KO (-/-) mice for analysis. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-09-30-161927.png\" style=\"height:926px; width:1716px\" class=\"size-full wp-image-52482\" /> Open field test comparing wild-type mice (C57BL/6N, blue) and <a href=\"http://biocytogen.com/products/induced-disease-model-mice/b-fmr1-ko-mice/\">B-Fmr1 KO mice</a> (teal). The total distance traveled (A), average speed (B), number of fecal pellets (C), time spent in the periphery (D) and center (E), as well as the number of crossings in the periphery (F) and center (G) were measured. B-Fmr1 KO mice exhibited significant hyperactivity compared to wild-type mice. Beyond the Basics: Custom and Drug-Targeted Humanized MiceBiocytogen offers customizable solutions that allow researchers to modify the mouse genome to meet their specific research needs. Our proprietary gene-editing technology can improve knock-in efficiency up to 20-fold compared to traditional CRISPR/Cas9, with a 98% success rate, enabling us to create reliable transgenic mouse strains in as little as 7 months. This advanced capability empowers researchers to explore hundreds of ASD-associated genes that have remained understudied due to the lack of suitable models. In addition, we provide cutting-edge humanized mouse models, in which mouse genes are replaced with their human counterparts, allowing researchers to study disease mechanisms in a human biological context. <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> today to learn how Biocytogen’s mouse models can accelerate your research! References<a href=\"https://doi.org/10.1098/rstb.2008.0328\">Howlin et al</a>. \"Savant skills in autism: psychometric approaches and parental reports.\" Philosophical Transactions of the Royal Society B: Biological Sciences 364.1522 (2009): 1359-1367.<a href=\"https://www.cdc.gov/mmwr/volumes/72/ss/ss7202a1.htm\">Maenner et al.</a> \"Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020.\" MMWR. Surveillance Summaries 72 (2023).<a href=\"https://journals.lww.com/jrms/fullt...ntal_factors_influencing_the_risk_of.27.aspx\">Karimi et al.</a> \"Environmental factors influencing the risk of autism.\" Journal of Research in Medical Sciences 22.1 (2017): 27.<a href=\"https://www.tandfonline.com/doi/full/10.3109/1547691X.2010.545086\">Ratajczak, Helen V.</a> \"Theoretical aspects of autism: Causes—A review.\" Journal of immunotoxicology 8.1 (2011): 68-79.<a href=\"https://gene.sfari.org/\">SFARI gene</a>: an evolving database for the autism research community that is centered on genes implicated in autism susceptibility.',1,'/neuroscience-autism-spectrum-disorder-mouse-model',0,2190,1728053604,646,'us,jp,kr',1728053604,0),(20,'Breaking the Diabesity Cycle: Unveiling New Research on Obesity and Diabetes','Animal Models','diabesity,diabetes,obesity','https://cdn.biocytogen.com/web/backend/upload/article/image/Obesity-and-Diabetes-1.png','Obesity and diabetes are two of the most pressing health challenges facing society today, impacting millions and often occurring hand in hand. As obesity rates have soared to epidemic levels, Type 2 diabetes has followed suit. While researchers have long known of this connection, only recently have they begun to uncover the complex mechanisms linking these conditions. The Connection Between Obesity and DiabetesDiabetes comes in two primary forms: Type 1, an autoimmune condition usually diagnosed in childhood, and Type 2, which often develops later in life due to lifestyle factors like diet and physical activity. Closely tied to obesity, Type 2 diabetes now affects millions in the U.S., with many more at risk as pre-diabetic (<a href=\"https://www.cdc.gov/diabetes/php/data-research/index.html\">CDC National Diabetes Statistics Report, 2024</a>).Obesity, defined by excess body fat and commonly measured by BMI, impacts over 40% of U.S. adults (<a href=\"https://www.cdc.gov/obesity/php/data-research/adult-obesity-facts.html\">CDC Obesity, 2024</a>). The rise in obesity rates has driven a parallel rise in Type 2 diabetes cases, a relationship so intertwined that experts have coined the term “diabesity” (<a href=\"https://www.obesityaction.org/resources/obesity-and-type-2-diabetes/\">Golay and Ybarra, 2005</a>).While not all individuals with diabetes are overweight, carrying excess weight significantly raises the risk of diabetes. Obesity contributes to Type 2 diabetes primarily by impacting insulin function; as body fat increases, cells become less responsive to insulin, leading to elevated blood sugar. Research indicates that people with obesity are three to seven times more likely to develop Type 2 diabetes, with severe obesity (BMI over 35) increasing this risk up to 20 times (<a href=\"https://www.obesityaction.org/resources/obesity-and-type-2-diabetes/\">Rogers and Still, 2009</a>). Animal Models for Diabetes and Obesity ResearchExciting new research is targeting the mechanisms connecting obesity and diabetes, with therapies aimed at reducing insulin resistance and fat-induced inflammation. Advanced animal models play a vital role in studying these conditions and how obesity affects insulin and blood sugar regulation, enabling scientists to explore potential therapies.Biocytogen’s specialized models, designed to replicate key aspects of obesity and diabetes, are driving progress and accelerating the development of effective therapies. High-Fat Diet-Induced Obese (DIO) Mouse ModelThe High-Fat DIO Mouse Model is a powerful tool for studying obesity-related metabolic disorders, including Type 2 diabetes. By consuming a diet composed of 60% kcal from fat, these mice develop key pathophysiological changes that closely resemble human conditions.<img alt=\"Characterization of High-Fat Diet-Induced Obese (DIO) Mouse Model.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-10-10-105416.png\" style=\"height:536px; width:1757px\" class=\"size-full wp-image-52693\" /> Characterization of High-Fat Diet-Induced Obese (DIO) Mouse Model. (A-B) Glucose tolerance after HFD induction. (B) Area under the curve for (A). (C-F) Blood biochemical analysis after HFD induction. Mean ± SEM, n=10 mice per group. Spontaneous Diabetes Model (B-ob/ob Mice, leptin deficient mice)The B-ob/ob mouse model is a specialized tool for studying obesity and high blood sugar (hyperglycemia). These mice lack exons 2 and 3 of the leptin gene, which is essential for maintaining energy balance and body weight.<img alt=\"Anti-obesity and Hypoglycemic Effects of Dulaglutide in B-ob/ob Mice. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-10-10-110549.png\" style=\"height:893px; width:844px\" class=\"size-full wp-image-52694\" />Anti-obesity and Hypoglycemic Effects of Dulaglutide in B-ob/ob Mice. (A-B) Body weight and blood glucose changes in B-ob/ob mice from 4 to 21 weeks of age. (C-F) Nine-week-old B-ob/ob mice received 1 mg/kg dulaglutide (in-house) twice weekly for 4 weeks. Body weight and blood glucose were recorded at the indicated times. Glucose tolerance tests were performed the day after the last dose (n = 8 mice per group). Drug-targeted humanized GLP1R mice (B-hGLP1R mice)GLP1R signaling enhances glucose-dependent insulin secretion, crucial for diabetes management. Biocytogen’s humanized GLP1R mouse model, with the mouse gene replaced by the human version, offers a powerful tool for in vivo evaluation of GLP1R-targeting drugs.<img alt=\"Efficacy Study of Semaglutide in HFD-Induced B-hGLP1R Mice. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-10-10-112445.png\" style=\"height:997px; width:1402px\" class=\"size-full wp-image-52695\" /> Efficacy Study of Semaglutide in HFD-Induced B-hGLP1R Mice. (A) Body weight change after HFD induction. (B-D) Body weight change following semaglutide treatment (an antidiabetic and anti-obesity medication for type 2 diabetes and long-term weight management). (E-F) Effect of semaglutide on food intake. (G) Blood glucose change after semaglutide treatment. (H) Glucose tolerance following treatment. (I) Area under the curve for (H). (J) Plasma insulin level. Mean ± SEM. N = 8–10 mice per group.  STZ-Induced Diabetes ModelThe STZ-induced diabetes model uses streptozotocin (STZ) to selectively destroy pancreatic β-cells, effectively mimicking type 1 diabetes. This model is essential for studying the disease and testing therapies targeting insulin production and blood glucose control.<img alt=\"Hypoglycemic Effect of GCGR Antibody in STZ-Induced B-hGCGR Mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-10-10-112916.png\" style=\"height:428px; width:1068px\" class=\"size-full wp-image-52696\" /> Hypoglycemic Effect of GCGR Antibody in STZ-Induced B-hGCGR Mice. (A-B) Body weight and blood glucose changes in 6-week-old B-hGCGR mice after STZ (50 mg/kg) induction. (C-D) Three weeks after STZ induction, GCGR antibody (10 mg/kg, produced in-house) was administered once per week. Non-fasting blood glucose (C) and fasting blood glucose (D) were measured. Mean ± SEM. Ready to make strides in diabetes and obesity research? <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> to explore how our advanced animal models can help drive your next breakthrough! References<a href=\"https://www.cdc.gov/diabetes/php/da...e-of-both-diagnosed-and-undiagnosed-diabetes\">CDC</a>, National Diabetes Statistics Report, 2024<a href=\"https://www.cdc.gov/obesity/php/data-research/adult-obesity-facts.html\">CDC</a>, Obesity, 2024<a href=\"https://www.obesityaction.org/resources/obesity-and-type-2-diabetes/\">Rogers, Joanne Z., and Christopher D. Still.</a> \"Obesity and type 2 diabetes.\" Obesity Action Coalition (OAC) (2009).<a href=\"https://pubmed.ncbi.nlm.nih.gov/16311223/\">Golay, Alain, and Juan Ybarra.</a> \"Link between obesity and type 2 diabetes.\" Best practice & research Clinical endocrinology & metabolism 19.4 (2005): 649-663.<a href=\"https://www.vincentrcmaribao.com/blog/heres-how-obesity-and-diabetes-are-connected\">Maribao, V.</a> (2023). Here’s How Obesity and Diabetes Are Connected.',1,'/obesity-diabetes-mouse-models',0,2210,1729197238,1301,'us,jp,kr',1729197238,0),(21,'Behind the Scenes: with Kareem: A Journey of Growth, Adventure, and Dedication at Biocytogen','Employee Story','','https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_3396.jpg','Meet Kareem, a key member of Biocytogen’s pharmacology team who brings a blend of passion, dedication, and a bit of adventure to everything he does. From fresh college graduate to a dedicated scientist, Kareem’s journey is a story of perseverance and learning. Outside the lab, he’s an outdoor enthusiast, spending weekends hiking to clear his mind and recharge. He’s also a self-proclaimed dog lover, with plans to adopt a medium-sized dog soon! And when he’s not on the trails, he’s practicing kickboxing for fun—gloves and all. Kareem’s adventurous side is what keeps him energized, both in life and in science.<img src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_3396.jpg\" />In the lab, Kareem’s days are action-packed as he manages everything from dosing and survival bleeds to tissue harvesting for pharmacokinetics (PK) studies. Working with genetically humanized mice requires focus, and Kareem’s attention to detail makes him a standout. One of his proudest moments was taking care of a large-scale PK study involving over 100 mice. He even found himself playing matchmaker, separating the dominant males to prevent fighting, and introduced exercise wheels to keep them entertained—turns out, mice need a good workout too! His proactive approach ensures smooth-running experiments and well-cared-for subjects.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_3397.jpg\" style=\"height:492px; width:724px\" class=\"aligncenter wp-image-52770\" />Kareem is proud of how Biocytogen’s commitment to quality assurance has shaped him as a scientist. The rigorous safety and QC checks have sharpened his skills and made him more detail-oriented. In his three years at the company, he’s learned the importance of collaboration, soaking up knowledge from his more experienced colleagues. For those looking to break into the biotech industry, Kareem’s advice is simple: stay motivated, learn fast, and embrace the fast-paced, ever-evolving world of biotech—just like he does with his kickboxing routine!<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/0K2A7139-1.jpg\" style=\"height:496px; width:712px\" class=\"aligncenter wp-image-52771\" />Kareem’s journey at Biocytogen is a powerful narrative of continuous growth, teamwork, and an unwavering drive to excel. His determination shines through both in the lab and his personal life, showcasing how passion fuels success. Whether he’s immersed in cutting-edge research or tackling challenges on hiking trails, Kareem embodies a proactive approach. His ability to balance professional responsibilities with personal interests keeps him energized and motivated, inspiring those around him. Kareem’s commitment to excellence reminds us that embracing challenges and fostering collaboration lead to remarkable achievements. With his adventurous spirit, he’s always ready to tackle the next challenge, proving that dedication knows no limits.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/0K2A2818-1.jpg\" style=\"height:462px; width:693px\" class=\"aligncenter wp-image-52772\" />',1,'/behind-the-scenes-with-kareem',0,2260,1729779886,459,'us,jp,kr',1729779886,0),(22,'GSK’s $300M Acquisition of Chimagen’s CMG1A46: A Deep Dive into B Cell-Targeted Trispecific T Cell Engagers','Industry Insights','B cell,Chimagen,CMG1A46,GSK,T cell,T cell engager,TCE,trispecific TCE','https://cdn.biocytogen.com/web/back...age/20241101-T-cell-and-B-cell-blog-cover.png','On October 29, GSK made headlines with a $300 million upfront payment to acquire Chimagen Biosciences’ clinical-stage asset, CMG1A46, a dual-target CD19/CD20 trispecific T cell engager (TCE). This acquisition signals GSK’s commitment to advancing therapies for B-cell-driven autoimmune diseases, such as systemic lupus erythematosus and lupus nephritis, with possible applications in other autoimmune conditions. B Cell Depletion Therapy in Autoimmune DiseasesB cell therapies are capturing growing interest as a promising approach to treating autoimmune diseases. B cells play a central role in these conditions, producing antibodies that mistakenly attack the body’s own tissues. B cell depletion therapy (BCDT) offers promising treatment options for conditions such as systemic lupus erythematosus, rheumatoid arthritis, and lupus nephritis. This approach involves selectively depleting, clearing, or inhibiting B cells at various stages of their lifecycle—development, maturation, and activation. Throughout their lifecycle, B cells express different surface antigens, such as CD19, CD20, CD38, CD138, BCMA, and BAFF. CD19, for example, appears across multiple stages, from Pro-B cells to plasma cells, while CD20 is found from Pre-B to memory B cells, making both ideal targets for B cell depletion therapies in autoimmune disease treatment.CMG1A46 is a trispecific antibody targeting CD19 and CD20 on B cells with high affinity and CD3 with low affinity. Preclinical studies show it effectively depletes B cells in blood and tissue while minimizing TCE toxicity, overcoming resistance issues in single-target therapies and showcasing strong therapeutic potential. B Cell-Related Drug-Targeted Humanized ModelsBiocytogen has pioneered the development of drug-targeted humanized mice carrying human CD3E and CD3EDG genes, along with B-cell-specific dual and multi-targets, creating powerful in vivo models for assessing TCE bispecific, trispecific, and multispecific antibodies in autoimmune disease research within a human biological context. Our portfolio also includes humanized mice targeting additional B cell-related proteins, such as CD40/CD40L and BAFF/BAFFR.<img alt=\"B Cell-Related Drug-Targeted Humanized Models at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-11-04-132508.png\" style=\"height:629px; width:500px\" class=\"aligncenter wp-image-52836\" /> Are Trispecific Antibodies the Next Frontier in Disease Treatment?By inhibiting multiple signaling pathways or targeting multiple cell types, bispecific and multispecific antibodies significantly enhance therapeutic efficacy. However, developing these antibodies presents challenges, particularly with chain mispairing during production. Our proprietary RenLite® mice, designed to generate antibodies with a common light chain, greatly reduce heavy and light chain mismatching during bispecific and multispecific antibody assembly. Paired with knobs-into-holes (KIH) technology, RenLite® achieves an assembly success rate of over 95%, simplifying the CMC process. The resulting bispecific antibodies from RenLite® mice retain structures similar to monoclonal antibodies and exhibit strong physicochemical properties. Using RenLite® KO mice, Biocytogen has developed an OX40 bispecific antibody, BCG028, for autoimmune disease therapy, demonstrating superior in vivo efficacy compared to traditional OX40 monoclonal antibodies. <img alt=\"Superior in vivo efficacy of BCG028-IgG1 and BCG028 in a mouse GvHD model\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Weixin-Image_20241106101237.jpg\" style=\"height:501px; width:1245px\" class=\"size-full wp-image-52855\" /> Superior in vivo efficacy of BCG028-IgG1 and BCG028 in a mouse model of chronic graft-versus-host disease (GvHD). Expanding on these advancements, Biocytogen, with its RenTCR-mimic™ platform, and CtM Bio, with its T-cell Engager platform, have jointly developed a WT1/HLA-A02-specific T cell engager (WT1xCD3x4-1BB tri-specific antibody). This project has achieved significant milestones, demonstrating impressive preclinical anti-tumor activity against both hematological malignancies and solid tumors. Looking ForwardDevelopment of bi- or tri-specific TCEs marks an exciting new chapter in the fight against various diseases, offering hope for more targeted, effective therapies. At Biocytogen, we’re committed to supporting this progress by equipping researchers with the advanced tools needed to accelerate discoveries and innovations.To explore how our drug-targeted humanized mouse models and antibody platforms can elevate your research, <a href=\"https://biocytogen.com/contact-us/\">request a demo and connect with our team today</a>!',1,'/gsks-cmg1a46-b-cell-targeted-trispecific-t-cell-engager-autoimmune',0,2270,1730747990,4302,'us,jp,kr',1730747990,0),(23,'Breaking Down Barriers in Drug Development: Key Takeaways from Biocytogen’s Maryland Forum','Industry Insights','','https://cdn.biocytogen.com/web/back...eixin-Image_20241029154334-e1730822203230.jpg','One of the biggest challenges in personalized medicine is not only proving efficacy but also ensuring feasible manufacturing at scale. Unlike traditional therapies developed for broader populations, personalized treatments are tailored for individuals, raising complex questions in CMC (Chemistry, Manufacturing, and Controls). How can production be controlled and scaled for drugs designed for individual patients?In a recent forum hosted by Biocytogen in Maryland, leading experts from biotech, biopharma, and the FDA gathered to discuss critical advancements in drug development. Panelists noted that developing customized drugs for individual patients requires a flexible CMC approach extending beyond proof of concept. For these therapies to succeed, feasibility and scalability at the CMC stage are essential.<h4>Early CMC Planning: A Must for Fast-Track Approvals</h4>With these challenges in mind, the discussion turned to the timing of CMC integration in the drug development process. Traditionally, the drug approval process spans about 10 years from discovery to final FDA approval, with CMC considerations introduced later, after efficacy and toxicity have been established. However, in today’s fast-paced landscape, more drugs are undergoing Fast Track FDA approval with significantly condensed timelines. Panelists pointed out the importance of integrating CMC planning early, ideally alongside initial efficacy and toxicology studies, to streamline clinical trial readiness and secure faster approval pathways, particularly through fast-track programs. This early integration ensures that drugs meet reproducibility and scalability requirements, potentially saving years in the approval process—averaging 5 years and sometimes as short as 3 years.<h4>FDA’s Role as a Development Partner</h4>FDA panelists highlighted a crucial mindset shift when approaching FDA interactions. Consulting with the FDA early and frequently, rather than waiting until filing submission, can provide invaluable guidance and potentially smooth the path toward regulatory approval. Establishing a collaborative relationship with the FDA can also help identify potential challenges early, saving both time and resources in the development process.<img class=\"aligncenter size-full wp-image-52842\" src=\"https://cdn.biocytogen.com/web/back...422336a394228c07bd6f18f7d9d0124-2-scaled.jpg\" alt=\"Maryland Biotech/Biopharma Forum by Biocytogen\" width=\"3000\" height=\"2250\" /><h4>AI in Clinical Trials: Transforming Data into Insights</h4>As one of the major advances in the field, the forum discussion explored AI’s role in drug development, particularly in analyzing clinical trial data. AI has the potential to enhance FDA trial design by learning from past successes and failures. With extensive data across numerous drug applications, including MOA and drug design, AI can be leveraged to identify patterns and suggest improvements. Though still evolving, AI shows promise as an “expert system” capable of accelerating the clinical trial learning curve, offering drug developers deeper insights.<h4>Broader Applications of CAR-T Cell Therapy</h4>While scaling up small molecule and antibody therapies is relatively straightforward in the CMC process, cell and gene therapies introduce a new level of complexity. For example, CAR-T cell therapy, traditionally focused on cancer, is now being explored for autoimmune diseases as well, highlighting the need for robust, scalable CMC frameworks tailored to cell-based therapies. Ensuring the feasibility of these advanced therapies at scale remains a major challenge—but it holds the promise of transformative options for patients with limited alternatives. <img class=\"aligncenter size-full wp-image-52843\" src=\"https://cdn.biocytogen.com/web/back...afe284fcd036f991-1-scaled-e1730822377733.jpg\" alt=\"Maryland Biotech/Biopharma Forum by Biocytogen\" width=\"3000\" height=\"1660\" />Dr. Dallas Files from NextCure sharing insights into the company’s pipeline at the forum.<h4></h4><h4>Looking Ahead</h4>The forum underscored the importance of rethinking traditional approaches to CMC, regulatory interactions, and data utilization to meet the demands of modern medicine. From integrating CMC early to embracing AI in clinical trials, each step represents an opportunity for the industry to innovate and streamline the path from lab to patient.Biocytogen is proud to have facilitated this dynamic exchange of ideas and remains committed to advancing discussions that bridge cutting-edge science and real-world applications.<img class=\"aligncenter wp-image-52844 size-full\" src=\"https://cdn.biocytogen.com/web/back...bc9d0b8b161b5f785cd16b843-e1730822554949.jpg\" alt=\"Maryland Biotech/Biopharma Forum by Biocytogen\" width=\"1706\" height=\"921\" />',1,'/drug-development-insights-fda-biocytogen-maryland-forum',0,2280,1730835688,619,'us,jp,kr',1730835688,0),(24,'The Future of Cancer Treatment: Cutting-Edge Advances in Immuno-Oncology','Industry Insights','adc,cancer,CAR-T,immune-checkpoints,immuno-oncology,oncology,T cell,TCE,treatment,tumor','https://cdn.biocytogen.com/web/back...age/20241031-T-cell-and-cancer-blog-cover.png','Imagine a future where cancer treatment is as precise and personalized as it is powerful, where the body’s own defenses are guided to hunt down and destroy tumors. This vision is becoming reality through immuno-oncology (IO), a transformative field empowering the immune system to selectively attack cancer cells. Unlike traditional treatments like chemotherapy and radiation, which can damage healthy cells, IO offers effective, less toxic therapies—setting a new standard in cancer care. Immune Checkpoint InhibitorsA major breakthrough in immuno-oncology is the development of immune checkpoint inhibitors (ICIs). Tumors can manipulate immune checkpoints, like PD-1/PD-L1 and CTLA-4, to evade the immune system’s attack. By “releasing the brakes” on T cell activity, ICIs enable a stronger immune response against tumors and have become standard therapies for cancers such as melanoma, NSCLC, bladder, and breast cancer. (<a href=\"https://ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00372-8#:~:text=This result, coupled with the,3).\">Ma et al., 2023</a>, <a href=\"https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors#:~:text=Immunotherapy drugs called immune checkpoint,checkpoint protein called CTLA-4.\">National Cancer Institute, 2022</a>).To advance this field, Biocytogen’s <a href=\"https://biocytogen.com/renmice-platforms/\">RenMice™ platform</a> has developed fully human monoclonal antibodies targeting immune checkpoints, with potential for development into ICI drugs. Additionally, Biocytogen’s drug-targeted humanized mouse models of immune checkpoints allow researchers to conduct in vivo evaluations of drug efficacy, toxicity, and PK/PD of checkpoint inhibitors against human targets, accelerating the discovery and delivery of innovative therapies to patients. Targeted Antibody ImmunotherapyAnother promising area in IO is targeted antibody immunotherapy, such as antibody-drug conjugates (ADCs) and T cell engagers (TCEs) (<a href=\"https://www.cancerresearch.org/treatment-types/targeted-antibodies\">Cancer Research Institute</a>). ADCs combine antibodies with potent drugs to deliver targeted treatment directly to cancer cells, while TCEs are bispecific or multispecific antibodies engineered to bind both immune cells and cancer cells, facilitating a direct immune attack on tumors.Biocytogen’s <a href=\"https://biocytogen.com/renmice-platforms/bsab-discovery-platform/\">RenLite® mice</a> address key challenges in developing these antibodies, such as chain mispairing during assembly. Combined with knobs-into-holes (KIH) technology, RenLite® achieves over 95% assembly success, supporting the development of fully human bispecific and multispecific antibody therapies. Our portfolio also includes BLD1102, a proprietary linker-payload system featuring the DNA topoisomerase I inhibitor BCPT02 and a highly hydrophilic, protease-cleavable linker, optimized for efficient ADC assembly.An example of Biocytogen\'s innovative approach is the WT1xCD3x4-1BB trispecific TCE. Developed collaboratively through Biocytogen’s <a href=\"https://biocytogen.com/renmice-platforms/tcr-mimic-antibody-platform/\">RenTCR-mimic™ platform</a>—focused on discovering high-affinity antibodies for intracellular antigens—and CtM Bio’s TCE platform, this TCE has demonstrated impressive preclinical anti-tumor activity in both hematological malignancies and solid tumors.<img alt=\"Dose-dependent anti-tumor efficacy of the WT1xCD3x4-1BB trispecific TCE (WT1-TOPAbody)\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-11-08-105715.png\" style=\"height:337px; width:636px\" class=\"wp-image-52891\" />Dose-dependent anti-tumor efficacy of the WT1xCD3x4-1BB trispecific TCE (WT1-TOPAbody) Biocytogen’s humanized mouse models further accelerate these therapies by enabling efficient preclinical testing against human targets in vivo. With models featuring single human targets, like ICIs and tumor microenvironment (TME) molecules, or multiple targets, such as CD3E/CD3EDG on T cells and tumor-associated antigens (TAAs) for evaluating TCEs, researchers can effectively assess IO-targeted antibodies. Biocytogen’s Humanized Mice for Immune Checkpoints, TME-Related, and Double or Multiple Targets<img alt=\"Biocytogen’s humanized mice for oncology research, targeting immune checkpoints, TME-related targets, and double or multiple candidates.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/WechatIMG116.jpg\" style=\"height:1195px; width:1927px\" class=\"size-full wp-image-52902\" /> Adoptive Cell TherapyAnother exciting advance in IO is adoptive cell therapy, especially CAR-T cell therapy. This approach involves extracting a patient’s own T cells, engineering them to express receptors that recognize cancer cells, and reintroducing them into the body (<a href=\"https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html\">American Cancer Society</a>). These CAR-T cells become “cancer hunters,” equipped to seek out and kill cancer cells with enhanced precision. Several CAR-T therapies have already received FDA approval for treating blood cancers (<a href=\"https://www.cancer.gov/about-cancer/treatment/research/car-t-cells\">National Cancer Institute, 2022)</a>. Biocytogen has extensive experience evaluating CAR-T cell efficacy across multiple tumor models, with reliable assessments conducted in our highly <a href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-mice/\">immunodeficient B-NDG mice</a>.<img alt=\"Establishment of a Raji Lymphoma Model in B-NDG Mice and Verification of CAR-T Therapy Efficacy\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Weixin-Image_20241108104712.png\" style=\"height:328px; width:817px\" class=\"size-full wp-image-52890\" /> Establishment of a Raji Lymphoma Model in B-NDG Mice and Verification of CAR-T Therapy Efficacy. B-luc-GFP Raji cells (5×10^5) were injected via tail vein of B-NDG mice, and tumor growth was monitored using small animal imaging. When tumor fluorescence reached ~1×10^6 p/sec, animals were divided into a control group and four treatment groups (n=6). CAR-T cells (1×10^7) were also injected via tail vein. (A) Tumor fluorescence intensity curve; (B) Body weight. Four CAR-T treatments differently inhibited tumor growth in B-NDG mice, highlighting B-NDG as a robust model for CAR-T efficacy verification. Mean ± SEM. Towards a Brighter Future Immuno-oncology aims not only to treat cancer but also to improve patients’ quality of life during and after therapy. With ongoing research, it promises more options, fewer side effects, and renewed hope. At Biocytogen, we\'re committed to advancing this field with cutting-edge models and resources, envisioning a future where each innovation brings more effective, manageable treatments and improved outcomes for patients. References<a href=\"https://ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00372-8#:~:text=This result, coupled with the,3).\">Ma, Weijie, et al.</a> \"Increasing cure rates of solid tumors by immune checkpoint inhibitors.\" Experimental Hematology & Oncology 12.1 (2023): 10.<a href=\"https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors#:~:text=Immunotherapy drugs called immune checkpoint,checkpoint protein called CTLA-4.\">National Cancer Institute</a>. \"Immune Checkpoint Inhibitors and Their Role in Cancer Treatment.\" (2022)<a href=\"https://www.cancerresearch.org/treatment-types/targeted-antibodies\">Cancer Research Institute</a>. “Targeted Antibodies and Immunotherapy.”<a href=\"https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html\">American Cancer Society</a>. \"CAR T-Cell Therapy.\"<a href=\"https://www.cancer.gov/about-cancer/treatment/research/car-t-cells\">National Cancer Institute</a>. \"CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers.\" (2022)<a href=\"https://www.cancer.gov/about-cancer/treatment/research/car-t-cells\"> </a>',1,'/immuno-oncology-cancer-treatment-checkpoint-inhibitors-adc-tce-cart',0,2300,1731085272,1320,'us,jp,kr',1731085272,0),(25,'How HLA Humanized Mice Are Transforming Preclinical Research and Immunotherapy','Animal Models','drug target humanized mouse,HLA,humanized mice,immune system,immunotherapy,vaccine development','https://cdn.biocytogen.com/web/backend/upload/article/image/Blog-cover-HLA-3.png','How does the immune system distinguish friend from foe? Human Leukocyte Antigens (HLAs) are key players in this process, acting as molecular \"spotlights\" that present peptide antigens to immune cells, triggering antibody production and the elimination of abnormal cells.HLA molecules are classified into two types:<ul><li>HLA Class I: Expressed on nearly all nucleated cells, these molecules present endogenous peptides, such as those derived from intracellular pathogens or tumor cells, to CD8+ cytotoxic T cells.</li><li>HLA Class II: Found on antigen-presenting cells (e.g., dendritic cells, macrophages, B cells), these molecules present exogenous peptides, originating from extracellular pathogens, to CD4+ helper T cells.</li></ul>Together, these HLA molecules not only form a versatile defense system against a wide range of threats, but also underpin advancements in modern medicine, shaping the effectiveness of vaccines and cutting-edge immunotherapies designed to harness the immune system to combat disease. Advancements and Applications of HLA Humanized MiceHLA humanized mice are transformative tools in immunological research. Engineered to express human HLA genes in place of their murine counterparts, these models enable the study of human-like immune responses in vivo, offering a clinically relevant platform for studying immune mechanisms and evaluating therapies in preclinical research.Biocytogen has developed a comprehensive suite of HLA humanized mice in both C57BL/6 and immunodeficient B-NDG backgrounds, facilitating preclinical testing of immune therapies, including cancer immunotherapies and vaccines, with high translational value. They are also pivotal for studying specific HLA alleles in autoimmune disease mechanisms and antigen-driven T-cell responses. Case Study: B-HLA-A2.1 MiceBiocytogen’s <a href=\"https://biocytogen.com/products/other-humanized-model/b-hla-a2-1-mice/\">B-HLA-A2.1 mice</a> express human α1 and α2 domains, which form the peptide-binding groove and determine antigen specificity, along with human β2-microglobulin, which ensures the structural integrity of the groove. This model generates robust immune responses that closely mimic those of humans to both peptide and mRNA vaccines, making it an excellent platform for evaluating vaccine candidates.<img alt=\"Antitumor activity of NY-ESO-1 peptides against syngeneic tumors. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-12-13-101659.png\" style=\"height:616px; width:1786px\" class=\"size-full wp-image-53168\" /> Antitumor activity of NY-ESO-1 peptides against syngeneic tumors. (A) Experimental scheme. (B) Prophylactic treatment with NY-ESO-1 peptides (300 µg) in B-HLA-A2.1 mice (n=6–8/group) reduced tumor growth after inoculation with B-HLA-A2.1/hNY-ESO-1 MC38 cells. (C) Body weight changes. B-HLA-A2.1 mice provide a powerful preclinical model for in vivo evaluation of vaccines. Mean ± SEM. <img alt=\"Antitumor activity of NY-ESO-1 mRNA vaccine against syngeneic tumors. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-12-13-101830.png\" style=\"height:588px; width:1800px\" class=\"size-full wp-image-53169\" /> Antitumor activity of NY-ESO-1 mRNA vaccine against syngeneic tumors. (A) Experimental scheme. (B) Therapeutic treatment with mRNA vaccine in B-HLA-A2.1 mice (n=6/group) implanted with B-HLA-A2.1/hNY-ESO-1 MC38 tumor cells showed robust tumor growth inhibition and prolonged survival. (C) Body weight changes. B-HLA-A2.1 mice serve as a powerful preclinical model for evaluating mRNA vaccines. Mean ± SEM. <img alt=\"Detection of vaccine-induced immune responses in B-HLA-A2.1 mice by IFN-γ ELISpot assay. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-12-13-101853.png\" style=\"height:601px; width:1757px\" class=\"size-full wp-image-53170\" /> Detection of vaccine-induced immune responses in B-HLA-A2.1 mice by IFN-γ ELISpot assay. (A) Vaccination and testing scheme. Male B-HLA-A2.1 mice (9–10 weeks old, n=3/group) were inoculated intramuscularly with PBS, LNP, or LNP-mRNA and vaccinated three times at 1-week intervals. Splenocytes were extracted one week after the final immunization, stimulated with peptides, NC, or PC, and IFN-γ secretion was measured. (B) Representative IFN-γ secretion results. (C) Summary of results. B-HLA-A2.1 mice serve as a robust preclinical model for vaccine evaluation. NC: negative control. PC: positive control. <img alt=\"LNP-mRNA vaccination generates specific effector CD8+ T cells in spleens. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-12-13-105619.png\" style=\"height:622px; width:1782px\" class=\"size-full wp-image-53172\" /> LNP-mRNA vaccination generates specific effector CD8+ T cells in spleens. Spleens from B-HLA-A2.1/hNY-ESO-1 MC38 tumor-bearing mice immunized with PBS, LNP, or LNP-mRNA were analyzed on day 27. Flow cytometry showed elevated percentages of spleen T cells (A) and CD8+ T cells (B) within CD45+ cells after LNP-mRNA treatment. LNP-mRNA generated tetramer+ CD8+ T cells (~50% of total CD8+ T cells) (E), predominantly in the effector memory subset (H) with reduced naïve (F) and central memory (G) subsets. IFN-γ secretion was mainly from CD8+ T cells (I) and not CD4+ T cells (J). <img alt=\"LNP-mRNA enhances beneficial repertoire of anti-tumor T cells. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2024-12-13-102155.png\" style=\"height:627px; width:1804px\" class=\"size-full wp-image-53171\" /> LNP-mRNA enhances the beneficial repertoire of anti-tumor T cells. Tumors from B-HLA-A2.1/hNY-ESO-1 MC38-bearing mice immunized with PBS, LNP, or LNP-mRNA were analyzed on day 27. Flow cytometry showed elevated tumor-infiltrating T cells (A) and CD8+ T cells (B) within CD45+ cells, while Tregs were reduced in the LNP-mRNA group (D). CD8+ T cells showed lower naïve (F) and increased effector memory (EM) subsets (H). IFN-γ production was observed in CD8+ T cells (I) and CD4+ T cells (J). HLA Humanized Mice on a C57BL/6 Background Available at Biocytogen<img alt=\"HLA humanized mice in c57bl/6 background at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/2-2-e1734374627253.png\" style=\"height:992px; width:1650px\" class=\"aligncenter size-full wp-image-53181\" />HLA Humanized Mice on a B-NDG Immunodeficient Background Available at Biocytogen<img alt=\"HLA humanized mice in B-NDG (immunodeficient) background at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/3-2-e1734374793311.png\" style=\"height:659px; width:1634px\" class=\"aligncenter size-full wp-image-53182\" /> What’s BeyondBy helping to bridge the gap between preclinical and clinical studies, HLA humanized mice facilitate the development of safer and more effective therapies, advancing progress in immunology and beyond. Biocytogen not only provides cutting-edge humanized models but also offers comprehensive pharmacological services using these models. <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> today to learn how our HLA-related products and services can accelerate your drug discovery journey!',1,'/hla-humanized-mice-preclinical-research-immunotherapy-vaccine-development',0,2400,1734108345,1659,'us,jp,kr',1734108345,0),(27,'COPD in Focus: Current Challenges and New Horizons in Treatment with Biocytogen’s Antibody Innovation','Antibody Assets','antibody,Chronic obstructive pulmonary disease,COPD,lung','https://cdn.biocytogen.com/web/backend/upload/image/blogs/202503261212119821.png','Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory condition that affects millions of lives worldwide. Characterized by airflow obstruction caused by chronic bronchitis and/or emphysema, COPD manifests through symptoms such as shortness of breath, excessive mucus production, and coughing (<a href=\"https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679\">Mayo Clinic, 2023</a>). Its prevalence continues to rise due to aging populations, smoking, and worsening air pollution.COPD is highly heterogeneous, varying significantly among patients (<a href=\"https://link.springer.com/article/10.1186/1479-5876-12-S2-S3\">Roca et al., 2014</a>). Chronic inflammation in the airways causes swelling, narrowing the airway lumen, and impairing respiration. The lungs, consisting of hundreds of millions of elastic alveoli, rely on their natural stretchability for efficient breathing. However, in COPD, damage to alveolar walls reduces elasticity, further compromising lung function (<a href=\"https://onlinelibrary.wiley.com/doi/full/10.1155/2012/542769\">Papandrinopoulou, Tzouda, & Tsoukalas, 2012</a>). Additionally, macrophages in COPD patients fail to effectively phagocytose bacteria, exacerbating pulmonary inflammation and contributing to disease progression (<a href=\"https://link.springer.com/article/10.1186/s12931-021-01718-8\">Singh et al., 2021</a>).Current treatments, such as bronchodilators and corticosteroids, manage symptoms but fail to address individual variations or control chronic complications. This highlights the urgent need for innovative therapeutic approaches. In 2024, significant progress was made in COPD therapy with two landmark FDA approvals. In June, Ohtuvayre, a novel inhaled treatment, was approved. On September 27, dupilumab (Dupixent) received approval as an add-on maintenance treatment for uncontrolled COPD with elevated eosinophil levels. These approvals mark critical milestones in the ongoing effort to improve outcomes for COPD patients. <img alt=\"Lung Changes in Patients with COPD (Adapted from Mayo Clinic, 2023)\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-110629.png\" style=\"height:521px; width:944px\" class=\"wp-image-53443\" /> Lung Changes in Patients with COPD (Adapted from <a href=\"https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679\">Mayo Clinic, 2023</a>) COPD-Related Assets at BiocytogenBiocytogen has established a sub-brand, <a rel=\"noopener\" href=\"https://biocytogen.com/renmice-platforms/\">RenBiologicsTM</a>, to explore global partnerships for an off-the-shelf library of over 400,000 fully human antibody sequences against approximately 1,000 targets, including COPD-related ones. Unlock the full potential of your research pipeline with Biocytogen’s unmatched fully human antibody library!<img alt=\"COPD-Related Assets at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Table-202501-e1736779453253.png\" style=\"height:1049px; width:1724px\" class=\"aligncenter size-full wp-image-53461\" /> Case Study: IGHE Antibody Developed by RenMabIGHE encodes the heavy chain constant region of IgE, consisting of CH1-CH4. Its interaction with the high-affinity receptor FCER1A triggers mast cell or basophil degranulation, the release of inflammatory mediators, and type I anaphylaxis. Anti-IgE therapies are indicated for conditions such as asthma, chronic spontaneous urticaria, and nasal polyps.The IGHE antibody, developed using our <a href=\"https://biocytogen.com/renmice-platforms/monoclonal-antibody-platform/\">RenMab</a> platform, effectively blocks IgE binding to both FCER1A and CD23, demonstrating affinities comparable to omalizumab analogs. Additionally, it exhibits cross-reactivity with human and monkey IgE, highlighting its potential for broad therapeutic applications. The Top 4 IGHE antibody clones can effectively block both FCER1A and CD23<img alt=\"The Top 4 IGHE antibody clones can effectively block both FCER1A and CD23\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-113440.png\" style=\"height:476px; width:1854px\" class=\"aligncenter size-full wp-image-53445\" /> Biocytogen\'s IGHE antibody clone exhibits higher affinity than omalizumab<img alt=\"Biocytogen\'s IGHE antibody clone exhibits higher affinity than omalizumab\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-113805.png\" style=\"height:295px; width:353px\" class=\"aligncenter wp-image-53446\" /> Case Study: MET Antibody Developed by RenNanoMET (cellular-mesenchymal epithelial transition factor) is a receptor tyrosine kinase that plays a critical role in promoting the malignant progression of cancer cells. Although MET is expressed in most normal tissues, it is highly overexpressed in tumors, making it a valuable tumor-specific target. Indications for MET-targeting therapies include non-small cell lung cancer (NSCLC) and solid tumors.Anti-MET monoclonal antibodies developed using our <a href=\"https://biocytogen.com/renmice-platforms/nanobodyplatform/\">RenNano</a> mice exhibit nanomolar-level affinity and internalization activity comparable to the benchmark. Internalization assay of our MET antibodies generated by RenNano<img alt=\"Internalization assay of our MET antibodies generated by RenNano.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-114617.png\" style=\"height:254px; width:882px\" class=\"aligncenter wp-image-53447\" /> Case Study: ST2 Antibody Developed by RenMabThe IL-33/ST2 signaling pathway is a key contributor to allergic reactions, asthma, and chronic inflammatory diseases. Our fully human ST2 antibodies, generated from the <a href=\"https://biocytogen.com/renmice-platforms/monoclonal-antibody-platform/\">RenMab</a> platform, demonstrate strong in vitro activity, with high affinity and cross-reactivity in humans and cyno. These antibody clones are classified into two distinct epitope bins, and all effectively block IL-33/ST2 reporter signaling in vitro, achieving IC50 values below 10 µg/mL. Inhibition of IL-33 signaling by our ST2 antibodies <img alt=\"Inhibition of IL-33 signaling by our ST2 antibodies.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-120257.png\" style=\"height:265px; width:589px\" class=\"aligncenter wp-image-53448\" /> Biocytogen\'s ST2 antibody clones show high affinity and a distinct epitope from the benchmark<img alt=\"Biocytogen\'s ST2 antibody clones show high affinity and a distinct epitope from the benchmark.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-10-120524.png\" style=\"height:297px; width:610px\" class=\"aligncenter wp-image-53449\" /> <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> to learn more about Biocytogen\'s COPD assets, fully human antibody library, and opportunities for evaluation, licensing, or co-development! References<a href=\"https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679\">Mayo Clinic</a>. COPD: Symptoms and causes.<a href=\"https://link.springer.com/article/10.1186/1479-5876-12-S2-S3\">Roca, Josep, et al.</a> \"Chronic obstructive pulmonary disease heterogeneity: challenges for health risk assessment, stratification and management.\" Journal of translational medicine 12 (2014): 1-11.<a href=\"https://onlinelibrary.wiley.com/doi/full/10.1155/2012/542769\">Papandrinopoulou, D., V. Tzouda, and G. Tsoukalas.</a> \"Lung compliance and chronic obstructive pulmonary disease.\" Pulmonary medicine 2012.1 (2012): 542769.<a href=\"https://link.springer.com/article/10.1186/s12931-021-01718-8\">Singh, R., et al.</a> \"Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD.\" Respiratory Research 22 (2021): 1-11.',1,'/blog-chronic-obstructive-pulmonary-disease-copd-challenge-and-treatment-renbiologics-antibody',0,2450,1736779464,1033,'us,jp,kr',1736779464,0),(30,'IL-2 & IL-15 Pathways: Charting a Bold Frontier in Oncology and Autoimmune Therapies with Biocytogen’s Advanced Mouse Models','Animal Models','autoimmune,cytokine,humanized mice,IL-15,IL-2,IL2,IL5,immunodeficient mice,Interleukin,oncology','https://cdn.biocytogen.com/web/backend/upload/article/image/Title-Here-3.png','The immune system is a complex network orchestrated by cytokines, which act as critical mediators of immune responses. Among them, IL-2 and IL-15, key members of the cytokine receptor γ-chain family, hold unique potential in tumor and autoimmune therapies. These type I four-helix bundle cytokines share several biological activities, including promoting the proliferation and activation of T cells and NK cells, inducing immunoglobulin synthesis in B cells, and supporting the differentiation of cytotoxic effector cells.IL-2 and IL-15 function as the immune system’s \"dual coaches.\" IL-2 manages both the “offense” (effector T cells and NK cells) and the “defense” (Treg cells) teams, ensuring a fine-tuned balance between immune activation and regulation (<a href=\"https://www.nature.com/articles/nri3156\">Boyman & Sprent, 2012</a>). In contrast, IL-15 focuses on preparing the “long-term strike force” (memory CD8+ T cells and NK cells) to maintain sustained readiness for extended challenges, particularly in combating tumors and infections (<a href=\"https://doi.org/10.1016/S1074-7613(00)80564-6\">Zhang et al., 1998</a>, <a href=\"https://doi.org/10.1182/blood-2003-08-2814\">Schluns, Klonowski, & Lefrançois, 2004</a>). IL-2: The Balancing ActPrimarily secreted by activated T cells, IL-2 binds to its three-part receptor complex (IL-2Rα/CD25, IL-2Rβ/CD122, IL-2Rγ/CD123), activating key signaling pathways such as JAK-STAT, PI3K/AKT, and MAPK/ERK to promote the proliferation of T cells and NK cells. In addition to stimulating effector T cells, IL-2 plays a crucial role in expanding regulatory T cells (Tregs), thereby maintaining a dynamic balance between immune activation and suppression (<a target=\"_blank\" rel=\"noopener\" href=\"https://www.mdpi.com/2072-6694/12/12/3586?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz-9cPOBmZ7xjBP6BzjppN15C4NxFZWn9JloSooIcZF8w2SOVj7a93CGVrrP4PK702sZ52c1W\">Yang & Lundqvist, 2020</a>). At low doses, IL-2 preferentially binds to the high-affinity IL-2Rβγ receptor, activating Treg cells and significantly improving immune tolerance in patients with autoimmune diseases. Conversely, at high doses, IL-2, after saturating Treg cells, engages receptors with moderate affinity, boosting the cytotoxicity of CD8+ T cells and NK cells.<img alt=\"IL2 signaling pathway\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IL2-pathway.png\" style=\"height:492px; width:474px\" class=\"wp-image-53473\" />IL-2 signaling pathway. Adapted from <a href=\"https://www.jci.org/articles/view/156628\">Holcomb & Zou, 2022</a>. IL-15: Sustained Immune ReadinessIL-15 is secreted by monocytes and macrophages, with its signaling relying on trans-presentation through IL-15Rα. While IL-15 shares receptor chains (IL-2Rβ and IL-2Rγ) with IL-2, leading to similar signaling pathways, it exhibits distinct biological properties. IL-15 primarily enhances the activity of memory CD8+ T cells and activates NK cell cytotoxicity, while exerting minimal effects on Treg cells. Unlike IL-2, IL-15 supports long-term immune surveillance, making it particularly advantageous for cancer immunotherapy and infectious disease treatments (<a href=\"https://doi.org/10.1158/2326-6066.CIR-15-0009\">Waldmann, 2015</a>). Moreover, its relatively low toxicity profile positions IL-15 as an ideal candidate for developing long-acting immune therapeutics.<img alt=\"IL-2 and IL-15 signaling pathways \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IL2IL5-pathway.png\" style=\"height:1104px; width:1342px\" class=\"size-full wp-image-53474\" /> IL-2 and IL-15 signaling pathways (<a href=\"https://www.mdpi.com/2072-6694/12/12/3586?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz-9cPOBmZ7xjBP6BzjppN15C4NxFZWn9JloSooIcZF8w2SOVj7a93CGVrrP4PK702sZ52c1W\">Yang & Lundqvist, 2020</a>) Biocytogen has developed a series of humanized and severely immunodeficient mice targeting IL-2, IL-15, and their signaling pathways. These models provide robust support for preclinical drug research and drive advancements in oncology and autoimmune therapy development. Case Study: <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2rb-il2rg-mice/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz--XQE279uI1zROyI9ccxyWLu5EVYM6VBgMIVBL2T59U0Stw69O2f2QFeAURiqNLeorN3KtD\">B-hIL2RB/hIL2RG Mice</a><img alt=\"Antitumor activity of IL-2 analogs (provided by the client) in B-hIL2RB/hIL2RG mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/B-hIL2RB_hIL2RG-mice-efficacy.png\" style=\"height:754px; width:922px\" class=\"wp-image-53475\" /> Antitumor activity of IL-2 analogs (provided by the client) in <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2rb-il2rg-mice/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz--XQE279uI1zROyI9ccxyWLu5EVYM6VBgMIVBL2T59U0Stw69O2f2QFeAURiqNLeorN3KtD\">B-hIL2RB/hIL2RG mice</a>. (A) MC38 tumor growth; (B) Body weight changes; (C) Tumor growth in the PBS-treated group; (D) Tumor growth in the IL-2 analog-treated group. MC38 cells were subcutaneously implanted in 8-week-old female B-hIL2RB/hIL2RG mice (n=5). Treatment with IL-2 analogs (red arrows) began when tumors reached ~100 mm³. IL-2 analogs effectively controlled tumor growth but caused some toxicity, leading to body weight loss and the death of some mice. B-hIL2RB/hIL2RG mice provide a valuable preclinical model for the in vivo evaluation of IL-2 therapeutics. Values are expressed as mean ± SEM. Case Study: <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil15-hil15ra-mice/\">B-hIL15/hIL15RA Mice</a><img alt=\"Effects of AMG-714 (in-house) in psoriasis-like skin lesions model of B-hIL15/hIL15RA mice. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/B-hIL15_hIL15RA-mice-efficacy.png\" style=\"height:820px; width:1458px\" class=\"size-full wp-image-53476\" /> Effects of AMG-714 (in-house) in the psoriasis-like skin lesions model of <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil15-hil15ra-mice/\">B-hIL15/hIL15RA mice</a>. (A-B) Body weight changes; (C-D) Daily erythema and scaling scores of the back (0–6); (E) Total score (erythema + scaling). IMQ-induced skin inflammation worsened and peaked by day 4. A 3 mg/kg anti-human IL-15 antibody improved erythema and scaling scores but had no effect on body weight. Case Study: <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2rb-hil2rg-hil15-hil15ra-mice/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz--XQE279uI1zROyI9ccxyWLu5EVYM6VBgMIVBL2T59U0Stw69O2f2QFeAURiqNLeorN3KtD\">B-hIL2RB/hIL2RG/hIL15/hIL15RA Mice</a><img alt=\"Antitumor activity of a long-acting IL-2 superkine (MDNA11 analog) in B-hIL2RB/hIL2RG/hIL15/hIL15RA mice.\" src=\"https://cdn.biocytogen.com/web/back...IL2RB_hIL2RG_hIL15_hIL15RA-mice-efficacy.png\" style=\"height:384px; width:1063px\" class=\"wp-image-53477\" /> Antitumor activity of a long-acting IL-2 superkine (MDNA11 analog) in <a href=\"https://biocytogen.com/products/humanized-cytokines_mice/b-hil2rb-hil2rg-hil15-hil15ra-mice/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz--XQE279uI1zROyI9ccxyWLu5EVYM6VBgMIVBL2T59U0Stw69O2f2QFeAURiqNLeorN3KtD\">B-hIL2RB/hIL2RG/hIL15/hIL15RA mice</a>. MC38 cells were subcutaneously implanted into homozygous mice (female, 6–7 weeks old, n=6). Treatment began when tumor volume reached ~50 mm³, with dosing and frequency shown in the panel. (A) MC38 tumor growth; (B) Body weight changes. MDNA11 analogs effectively controlled tumor growth. These mice provide a robust preclinical model for in vivo evaluation of IL-2 therapies. Values are expressed as mean ± SEM. (The experiment was verified by the partner, and the drugs used belong to the client. MDNA11 analog does not bind to human IL-2RA but exhibits higher affinity for human IL-2RB.) IL-2 and IL-15 Related Mouse Models at Biocytogen<img alt=\"IL-2 and IL-15 Related Mouse Models at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-14-100917.png\" style=\"height:902px; width:698px\" class=\"aligncenter size-full wp-image-53478\" /> <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> to learn more about Biocytogen\'s humanized and severely immunodeficient mice targeting IL-2, IL-15, and their receptor pathways! References<a href=\"https://www.nature.com/articles/nri3156\">Boyman, Onur, and Jonathan Sprent.</a> \"The role of interleukin-2 during homeostasis and activation of the immune system.\" Nature Reviews Immunology 12.3 (2012): 180-190.<a href=\"https://doi.org/10.1016/S1074-7613(00)80564-6\">Zhang, Xiaohong, et al</a>. \"Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15.\" Immunity 8.5 (1998): 591-599.<a href=\"https://doi.org/10.1182/blood-2003-08-2814\">Schluns, Kimberly S., Kimberly D. Klonowski, and Leo Lefrançois</a>. \"Transregulation of memory CD8 T-cell proliferation by IL-15Rα+ bone marrow–derived cells.\" Blood 103.3 (2004): 988-994.<a href=\"https://www.mdpi.com/2072-6694/12/12/3586\">Yang, Ying, and Andreas Lundqvist.</a> \"Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy.\" Cancers 12.12 (2020): 3586.<a href=\"https://www.jci.org/articles/view/156628\">Holcomb, Erin A., and Weiping Zou</a>. \"A forced marriage of IL-2 and PD-1 antibody nurtures tumor-infiltrating T cells.\" The Journal of Clinical Investigation 132.3 (2022).<a href=\"https://doi.org/10.1158/2326-6066.CIR-15-0009\">Waldmann, Thomas A</a>. \"The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy.\" Cancer immunology research 3.3 (2015): 219-227.',1,'/blog-il2-il15-immunotherapy-oncology-autoimmune-humanized-mice',0,2470,1737490744,2516,'us,jp,kr',1737490744,0),(31,'TL1A Pathway: Embarking on New Frontiers in IBD Therapy with Biocytogen’s Humanized Mice','Animal Models','Autoimmune and Inflammatory Diseases,DR3,humanized mice,IBD,inflammatory bowel diseases,TL1A,TNFSF15','https://cdn.biocytogen.com/web/backend/upload/article/image/Title-Here-4.png','On December 17, Sanofi’s TL1A antibody, duvakitug, demonstrated success in a Phase IIb study, improving clinical remission rates in patients with moderate to severe ulcerative colitis and Crohn’s disease. Currently, several TL1A inhibitors—including monoclonal and bispecific antibodies such as tulisokibart, PF-07261271, and FG-M701—are in development to address unmet needs in the treatment of inflammatory bowel diseases (IBD). Current TL1A Pipeline of Leading Multinational Corporations (MNCs)<img alt=\"Current TL1A Pipeline of Leading Multinational Corporations (MNCs)\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-16-101702.png\" style=\"height:451px; width:1184px\" class=\"aligncenter size-full wp-image-53539\" />TL1A (TNF-like cytokine 1A), encoded by the TNFSF15 gene, is a member of the TNF superfamily. By binding to death receptor 3 (DR3), TL1A activates pathways involved in cell proliferation, apoptosis, and cytokine production, playing a key role in maintaining the balance between innate and adaptive immune homeostasis.<img alt=\"TL1A in Chronic Colitis. (Source: Takedatsu et al., 2008)\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/nihms65164f8.jpg\" style=\"height:561px; width:600px\" class=\"wp-image-53540\" /> TL1A in Chronic Colitis. (Source: <a href=\"https://doi.org/10.1053/j.gastro.2008.04.037\">Takedatsu et al., 2008</a>) (A) Chronic colitis compromises the intestinal epithelial barrier, allowing gut bacteria to penetrate the lamina propria (LP) and stimulate antigen-presenting cells (APCs). Stimulation of APCs, LP macrophages, or dendritic cells (DCs) upregulates TL1A, which enhances the ability of IL-12 and IL-23 to promote TH1 and TH17 cell activation, leading to excessive cytokine production and worsening inflammation. (B) Anti-TL1A antibodies reduce IFN-γ, IL-17, and IL-6 secretion, alleviating inflammation while maintaining bacterial clearance. TL1A is abnormally overexpressed in several autoimmune diseases, where it plays a significant role in the pathogenesis of conditions such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases (IBD). Its unique mechanism of action positions it as a critical factor in both inflammatory responses and immune regulation. In the context of IBD, including ulcerative colitis and Crohn’s disease, TL1A has emerged as a highly promising therapeutic target, drawing considerable attention for its potential in treatment strategies. TL1A-Related Mouse Models at BiocytogenBiocytogen has developed a series of humanized mouse models targeting TL1A signaling pathways and established stable IBD models using diverse induction methods across various genetic backgrounds. These models support preclinical research and efficacy evaluation in IBD.<img alt=\"TL1A-related mouse models at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-16-101619.png\" style=\"height:353px; width:600px\" class=\"aligncenter wp-image-53541\" /> Case Study: <a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htl1a-mice/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz-9kNpKeN2_da28N8CPESk0WZyM239aDOvsX6ctMzjc-F53D6AGRacFanmF0nXeyKyB-RDV9\">B-hTL1A Mice</a> Protein expression analysis<img alt=\"Soluble human TL1A expression in B-hTL1A mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-23-140408.png\" style=\"height:272px; width:591px\" class=\"wp-image-53542\" />Soluble human TL1A was detected exclusively in the supernatant of bone marrow-derived dendritic cells (BMDCs) stimulated from homozygous B-hTL1A mice, with no detection in wild-type mice. TNBS-induced acute colitis in B-hTL1A mice<img alt=\"TNBS-induced acute colitis in B-hTL1A mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-16-165157.png\" style=\"height:1191px; width:774px\" class=\"wp-image-53543\" /> An cute colitis model was established in B-hTL1A mice (female, 8–10 weeks old, n=8) by TNBS instillation, with PBS as a control (Sham). The anti-human TL1A antibody, Tulisokibart (PRA023, 25 mpk, provided by WuXi AppTec), was administered to the treatment group. Body weight and DAI score were recorded daily. On day 5, the mice were sacrificed, and colon length and weight were recorded. Colon tissue was later processed for H&E and Masson staining. (A) Body weight change. (B) DAI score. (C) Colon Index. (D) Pathological score. (E) Masson staining score. Tulisokibart effectively improved TNBS-induced colitis, demonstrating B-hTL1A mice as a robust model for evaluating anti-human TL1A antibodies. (Study conducted by WuXi AppTec) DSS-induced acute colitis in B-hTL1A mice<img alt=\"DSS-induced acute colitis in B-hTL1A mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-17-144529.png\" style=\"height:957px; width:1141px\" class=\"size-full wp-image-53544\" /> B-hTL1A mice (female, 7–8 weeks old, n=8) were given drinking water containing DSS for 9 consecutive days to induce an acute colitis model. The anti-human TL1A antibody, Tulisokibart (PRA023, 25 mpk, provided by WuXi AppTec), was administered to the treatment group. Body weight changes and clinical scores (weight loss, stool consistency, blood in stool, and total DAI score) were recorded throughout the experiment. On day 8, the mice were sacrificed, and colon length and weight were measured. (A) Body weight change. (B) DAI score. (C) Colon Index. Tulisokibart improved the clinical symptoms of DSS-induced acute colitis, demonstrating that B-hTL1A mice are a robust model for evaluating the in vivo efficacy of anti-human TL1A antibodies. (Study conducted by WuXi AppTec) Case Study: <a href=\"https://biocytogen.com/products/humanized-immune-checkpoint-mice/b-htl1a-hil23a-hil12b-mice-2/?utm_campaign=Email Marketing&utm_source=hs_email&utm_medium=email&_hsenc=p2ANqtz-9kNpKeN2_da28N8CPESk0WZyM239aDOvsX6ctMzjc-F53D6AGRacFanmF0nXeyKyB-RDV9\">B-hTL1A/hIL23A/hIL12B Mice</a> Protein expression analysis<img alt=\"Soluble human TL1A and IL-23 were detected exclusively in the supernatant of bone marrow-derived dendritic cells (BMDCs) stimulated from homozygous B-hTL1A/hIL23A/hIL12B mice, with no detection in wild-type mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-23-142145.png\" style=\"height:224px; width:798px\" class=\"wp-image-53545\" /> Soluble human TL1A and IL-23 were detected exclusively in the supernatant of bone marrow-derived dendritic cells (BMDCs) stimulated from homozygous B-hTL1A/hIL23A/hIL12B mice, with no detection in wild-type mice. DSS-induced IBD mouse model in B-hTL1A/hIL23A/hIL12B mice<img alt=\"DSS-induced IBD mouse model in B-hTL1A/hIL23A/hIL12B mice\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-23-142904.png\" style=\"height:1025px; width:958px\" class=\"size-full wp-image-53546\" /> A TNBS-induced acute colitis model in B-hTL1A/hIL23A/hIL12B mice demonstrated improved outcomes with anti-human TL1A antibody Tulisokibart and anti-human IL23p19 antibody Risankizumab, with enhanced efficacy when combined. Results highlight B-hTL1A/hIL23A/hIL12B mice as a valuable tool for evaluating the in vivo efficacy of these antibody combinations. (Study conducted by WuXi AppTec). There’s MoreIn addition to TL1A-related mouse models, Biocytogen has developed humanized models targeting other IBD-related pathways, as well as chemical-induced and adoptive transfer models of IBD. We also offer pharmacology services to support clinical evaluations and pathological analyses. List of IBD-related targeted humanized mice at Biocytogen<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-16-101644.png\" style=\"height:722px; width:1219px\" class=\"aligncenter size-full wp-image-53547\" /> IBD models and pharmacology services at Biocytogen<img alt=\"Other IBD Models and Pharmacology Services at Biocytogen\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-01-24-113005.png\" style=\"height:340px; width:1256px\" class=\"aligncenter size-full wp-image-53551\" /> <a href=\"https://biocytogen.com/contact-us/\">Contact us</a> to learn more about Biocytogen\'s IBD-related models and services! References<a href=\"https://www.nature.com/articles/nri3156\">Boyman, Onur, and Jonathan Sprent.</a> \"The role of interleukin-2 during homeostasis and activation of the immune system.\" Nature Reviews Immunology 12.3 (2012): 180-190.<a href=\"https://doi.org/10.1016/S1074-7613(00)80564-6\">Zhang, Xiaohong, et al</a>. \"Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15.\" Immunity 8.5 (1998): 591-599.<a href=\"https://doi.org/10.1182/blood-2003-08-2814\">Schluns, Kimberly S., Kimberly D. Klonowski, and Leo Lefrançois</a>. \"Transregulation of memory CD8 T-cell proliferation by IL-15Rα+ bone marrow–derived cells.\" Blood 103.3 (2004): 988-994.<a href=\"https://www.mdpi.com/2072-6694/12/12/3586\">Yang, Ying, and Andreas Lundqvist.</a> \"Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy.\" Cancers 12.12 (2020): 3586.<a href=\"https://www.jci.org/articles/view/156628\">Holcomb, Erin A., and Weiping Zou</a>. \"A forced marriage of IL-2 and PD-1 antibody nurtures tumor-infiltrating T cells.\" The Journal of Clinical Investigation 132.3 (2022).<a href=\"https://doi.org/10.1158/2326-6066.CIR-15-0009\">Waldmann, Thomas A</a>. \"The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy.\" Cancer immunology research 3.3 (2015): 219-227.',1,'/blog-tl1a-tnfsf15-ibd-inflammatory-bowel-disease-humanized-mouse-model',0,2490,1738093712,8554,'us,jp,kr',1738093712,0),(33,'B-NDG hIL15 Mice: Where Enhanced Human Immune Reconstitution Fuels NK-Dependent Therapies','Animal Models','B-NDG,B-NDG hIL15,CDX,HSC,IL15,NK cell,oncology,PBMC,PDX,reconstitution','https://cdn.biocytogen.com/web/backend/upload/article/image/Title-Here.png','Highly immunodeficient mouse models enable human immune system reconstitution, allowing the engraftment of human tissues or cells for research on immune function, therapeutic efficacy, and disease modeling. While these models effectively reconstitute human T cells, the lack of human IL15—an essential cytokine for NK cell maturation—hinders human NK cell reconstitution, limiting research on NK cell biology and the evaluation of NK-dependent immunotherapies (<a href=\"https://doi.org/10.1182/blood-2021-150593\">Gergues et al., 2021</a>; <a href=\"https://www.nature.com/articles/s41421-022-00467-2\">Huang et al., 2022</a>; <a href=\"https://www.cell.com/cancer-cell/fu...33369ab228403c922dcb5087c88d85&elqTrack=true\">Liu et al., 2023</a>).<div>To address this challenge, Biocytogen developed <a rel=\"noopener\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/b-ndg-hil15-mice/\">B-NDG hIL15 mice</a>, an IL15-humanized model based on our highly immunodeficient <a rel=\"noopener\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/\">B-NDG mice</a>. This advanced model expresses human IL15 but not mouse IL15, providing the necessary cytokine support for NK cell development. It significantly improves human NK cell reconstitution, making B-NDG hIL15 mice a powerful tool for studying NK cells and evaluating NK-dependent therapies. <img alt=\"IL15 in human NK cell development\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Picture3.jpg\" style=\"height:248px; width:576px\" class=\"wp-image-53587\" /> IL15 in human NK cell development. (Source: <a rel=\"noopener\" style=\"font-style: italic;\" href=\"https://doi.org/10.1182/blood.V97.1.14\">Fehniger & Caligiuri, 2001</a>) </div><img alt=\"Strain-specific IL15 expression in B-NDG and B-NDG hIL15 mice. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-112715.png\" style=\"height:307px; width:1071px\" class=\"wp-image-53596\" /> Strain-specific IL15 expression in B-NDG and B-NDG hIL15 mice. Serum from wild-type B-NDG (+/+), heterozygous (H/+), and homozygous (H/H) B-NDG hIL15 mice (male, 6 weeks old) was analyzed by ELISA after in vivo poly(I:C) stimulation. Human IL15 was detectable in B-NDG hIL15 mice but not in B-NDG mice. B-NDG hIL15 Mice Enhance Human NK Cell ReconstitutionUpon engrafting human CD34+ hematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs), or NK cells, B-NDG hIL15 mice showed a significant increase in both the frequency and absolute number of reconstituted human NK cells compared to B-NDG mice. Other immune cells like T cells, B cells, and myeloid cells also exhibited enhanced reconstitution. Human CD34+ HSC-reconstituted modelWhen human HSCs were engrafted into B-NDG hIL15 mice (huHSC-B-NDG hIL15 mice), the reconstitution of human NK cells was significantly improved in both adult and newborn mice compared with B-NDG mice. Human CD34+ HSC engraftment in B-NDG hIL15 mice (adult) enhances human NK cell reconstitution<img alt=\"Human immune cell phenotyping in B-NDG hIL15 mice engrafted with human HSCs.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-100417.png\" style=\"height:609px; width:1632px\" class=\"size-full wp-image-53588\" /> Human immune cell phenotyping in B-NDG hIL15 mice engrafted with human HSCs. Human CD34+ cells were intravenously injected into irradiated (1.6 Gy) homozygous B-NDG hIL15 (n=19) and B-NDG mice (n=17), both female and 6 weeks old. Flow cytometry of peripheral blood lymphocytes showed a higher percentage of human NK cells in B-NDG hIL15 mice. Human NK, T, and B cells were successfully propagated. Human CD34+ HSC engraftment in B-NDG hIL15 mice (neonatal) enhances the reconstitution of human NK cells and other immune cells like T cells, B cells, and myeloid cells<img alt=\"Engraftment of human CD34+ HSCs in neonatal B-NDG hIL15 mice successfully reconstituted human immune cells.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Picture5.png\" style=\"height:760px; width:1708px\" class=\"size-full wp-image-53582\" /> Engraftment of human CD34+ HSCs in neonatal B-NDG hIL15 mice successfully reconstituted human immune cells. Human CD34+ HSCs were engrafted via the facial vein into irradiated B-NDG hIL15 and B-NDG mice (24–48 hours old). Peripheral blood immune cell reconstitution was analyzed by flow cytometry. (A) Survival curve; (B) Body weight; (C) Percentages and numbers of human immune cells. huHSC-B-NDG hIL15 mice exhibited significantly higher percentages of human CD45+ and NK cells, along with greater numbers of CD45+, T, B, NK, and myeloid cells. NK cells isolated from the spleen of huHSC-B-NDG hIL15 mice possess tumor-killing activity against Jurkat cells<img alt=\"NK cells from huHSC-B-NDG hIL15 mice exhibit tumor-killing activity against Jurkat cells.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-100016.png\" style=\"height:870px; width:1596px\" class=\"size-full wp-image-53589\" /> NK cells isolated from huHSC-B-NDG hIL15 mice exhibit tumor-killing activity against Jurkat cells. Spleen-derived NK cells were collected 14 weeks after hCD34+ HSC engraftment (n=4) and assessed via LDH assay. Human PBMC-purified NK cells served as a positive control. (A) Reconstituted human CD45+ cells ranged from 56% to 81%. (B) Reconstituted human NK cell counts ranged from 22 to 44 cells/µL of blood. (C) The cytotoxicity of reconstituted human NK cells was comparable to that of PBMC-derived NK cells. (D-F) Activity markers of NK cells were analyzed by flow cytometry. NK cells expressing hCD69, hCD107a, and hGranzyme B were detected in reconstituted NK cells. After incubation with Jurkat cells, the proportion of NK cells expressing hCD69 and hCD107a increased, while hGranzyme B levels remained unchanged. Compared to PBMC-derived NK cells, the proportion of reconstituted NK cells expressing hCD69 and hCD107a was lower, whereas the proportion of cells expressing hGranzyme B was higher. These results indicate that reconstituted human NK cells in huHSC-B-NDG hIL15 mice exhibit cytotoxicity comparable to that of human NK cells purified from PBMCs. B-NDG hIL15 mice exhibit a high and stable reconstitution rate of human CD34+ HSCs<img alt=\"Reconstitution of Human CD34+ HSCs from Different Donors. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-100044.png\" style=\"height:1032px; width:1405px\" class=\"size-full wp-image-53590\" /> Reconstitution of Human CD34+ HSCs from Different Donors. (A) Human CD34+ HSCs engrafted in newborn B-NDG hIL15 mice stably reconstitute immune cells, with success rates varying by donor. (B) Mouse survival rate ranges from 80% to 90% at 24 weeks post-reconstitution. (C) Mice continue to gain weight after reconstitution. Human PBMC-reconstituted model<img alt=\"Human immune cell phenotyping in B-NDG hIL15 mice engrafted with human PBMC.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-100253.png\" style=\"height:860px; width:1636px\" class=\"size-full wp-image-53593\" /> Human immune cell phenotyping in B-NDG hIL15 mice engrafted with human PBMC. Human PBMCs were intravenously implanted into B-NDG hIL15 (n=15) and B-NDG (n=10) female mice (5 weeks old). Blood was collected at different time points for flow cytometric analysis. (A) Human immune cell phenotyping, (B) NK cell phenotyping, (C) Survival, (D) Body weight. Results indicate successful propagation of human NK and T cells in reconstituted B-NDG hIL15 mice. Human NK cell-reconstituted model<img alt=\"Engraftment of human NK cells in B-NDG hIL15 mice enhanced human NK cell reconstitution.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-100125.png\" style=\"height:317px; width:844px\" class=\"wp-image-53594\" /> Engraftment of human NK cells in B-NDG hIL15 mice enhanced human NK cell reconstitution. Irradiated B-NDG (n=7) and B-NDG hIL15 (n=8) mice (6 weeks old) were intravenously injected with purified human NK cells from PBMCs. Peripheral blood was analyzed weekly. NK cells purified from PBMCs reached 80%, and the number and proportion of reconstituted NK cells (CD3⁻CD56⁺) were significantly higher in B-NDG hIL15 mice. The NK cell proportion remained ~80% after 2 weeks and stayed higher after 6 weeks. Reconstituted NK cells were predominantly CD16⁺ NK cells with cytotoxic activity. Applications in Preclinical Oncology ResearchWe have successfully established various cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models using <a rel=\"noopener\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/huhsc-b-ndg-hil15-mice/\">HSC-</a>, PBMC-, or <a rel=\"noopener\" href=\"https://biocytogen.com/products/immunodeficient-b-ndg-mice/hunk-b-ndg-hil15-mice/\">NK cell-</a>reconstituted B-NDG hIL15 mice, enabling in vivo evaluation of therapeutics in a humanized immune environment. These models have been leveraged to assess antibodies such as anti-human CLDN18.2 and anti-human CD3×HER2 bispecific antibodies, demonstrating their effectiveness in suppressing tumor growth. In vivo efficacy of anti-human CLDN18.2 antibody in CDX model established with huHSC-B-NDG hIL15 mice <img alt=\"Antitumor activity of anti-human CLDN18.2 antibody (Zolbetuximab) in a lung cancer A549 CDX model established with huHSC-B-NDG hIL15 mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Picture3.png\" style=\"height:660px; width:1371px\" class=\"wp-image-53578\" /> Antitumor activity of anti-human CLDN18.2 antibody (Zolbetuximab) in a lung cancer A549 CDX model established with huHSC-B-NDG hIL15 mice. Human CD34+ HSCs were intravenously engrafted into irradiated B-NDG hIL15 mice. When hCD45+ cells exceeded 25% in blood, B-hCLDN18.2 A549 cells were subcutaneously inoculated. Mice were grouped at 80-100 mm³ tumor volume and treated with zolbetuximab. Zolbetuximab effectively inhibited tumor growth, with high levels of human NK cells detected in blood and tumor tissues. In vivo efficacy of anti-human CD3×HER2 BsAb in PDX model established with huHSC-B-NDG hIL15 mice <img alt=\"Antitumor activity of anti-human CD3×HER2 BsAb in a pancreatic cancer PDX model established with huHSC-B-NDG hIL15 mice. \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Picture2.png\" style=\"height:358px; width:965px\" class=\"wp-image-53579\" /> Antitumor activity of anti-human CD3×HER2 BsAb in a pancreatic cancer PDX model established with huHSC-B-NDG hIL15 mice. Human CD34+ HSCs were engrafted into irradiated B-NDG hIL15 mice. Pancreatic cancer PDX (BP0209) was inoculated, and mice were grouped at 100-150 mm³ tumor volume for intraperitoneal CD3×HER2 BsAb treatment. Treatment effectively inhibited tumor growth. In vivo efficacy of anti-human CLDN18.2 antibody in CDX model established with huNK-B-NDG hIL15 mice <img alt=\"Antitumor activity of anti-human CLDN18.2 antibody in A549 CDX model established with huNK-B-NDG hIL15 mice.\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-03-110858.png\" style=\"height:792px; width:1621px\" class=\"size-full wp-image-53595\" /> Antitumor activity of anti-human CLDN18.2 antibody in A549 CDX model established with huNK-B-NDG hIL15 mice. Human NK cells from PBMCs were intravenously engrafted into X-ray-irradiated B-NDG hIL15 mice. B-hCLDN18.2 A549 cells were subcutaneously inoculated. Mice were grouped when tumors reached ~100–150 mm³ and treated with zolbetuximab (n=6). Peripheral blood was collected weekly to assess human CD45⁺ and NK cell reconstitution. Results showed zolbetuximab effectively inhibited tumor growth, with high levels of human NK cells detected in peripheral blood. Humanized Mouse Models for NK-Dependent Therapies<img alt=\"Product List related to B-NDG hIL15 \" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Screenshot-2025-02-02-at-6.png\" style=\"height:279px; width:619px\" class=\"aligncenter wp-image-53576\" />Ready to accelerate your NK cell studies? <a rel=\"noopener\" href=\"https://biocytogen.com/contact-us/\">Contact us</a> to learn more! References<a href=\"https://doi.org/10.1182/blood-2021-150593\">Gergues, Marina, et al.</a> \"Development of CD19 CAR Engineered Human Placental CD34+-Derived Natural Killer Cells (CAR19-CYNK) As an Allogeneic Cancer Immunotherapy.\" Blood 138 (2021): 2779.<a href=\"https://www.nature.com/articles/s41421-022-00467-2\">Huang, Dehao, et al.</a> \"Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells.\" Cell Discovery 8.1 (2022): 121.<a href=\"https://www.cell.com/cancer-cell/fu...33369ab228403c922dcb5087c88d85&elqTrack=true\">Liu, Xiaowei, et al.</a> \"Immune checkpoint HLA-E: CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance.\" Cancer Cell 41.2 (2023): 272-287.<a href=\"https://doi.org/10.1182/blood.V97.1.14\">Fehniger, Todd A., and Michael A. Caligiuri.</a> \"Interleukin 15: biology and relevance to human disease.\" Blood, The Journal of the American Society of Hematology 97.1 (2001): 14-32.',1,'/blog-bndg-il15-nk-cell-immune-reconstitution-immunodeficient-oncology-therapy',0,2500,1738606056,1310,'us,jp,kr',1738606056,0),(34,'Behind the Scenes: Meet Hannah: A Journey Through Business Development with a Twist','Employee Story','','https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260039329599.jpg','Looking for someone who blends science, strategy, and a touch of fun? Meet Hannah, a standout in Biocytogen’s business development team. Alongside her stellar work, she’s a dedicated cat lover and passionate yoga instructor. Teaching yoga helps her unwind after a day full of strategic thinking—“A good stretch is the perfect balance!” she says. With a Ph.D. and a knack for turning challenges into opportunities, Hannah’s energy and expertise make her a unique asset both in the office and on the mat.<div class=\"flex flex-col flex-grow max-w-full\"><div dir=\"auto\" class=\"[.text-message+&]:mt-5 break-words flex flex-col gap-2 items-end min-h-[20px] overflow-x-auto text-message w-full whitespace-normal\"><div class=\"empty:hidden first:pt-[3px] flex flex-col gap-1 w-full\"><div class=\"break-words dark:prose-invert light markdown prose w-full\">Hannah and Yzma! Yzma enjoys watching reality TV and eating plants.</div></div></div></div><img src=\"https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260039329599.jpg\" />The Hannah Approach to Business Development Every day for Hannah at Biocytogen is like balancing a complex yoga pose—exactly what makes her job so exciting! Whether she’s connecting the dots between clients from Chicago to Boston and to Beijing or managing the intricate dynamics within various organizational structures, Hannah is on it. What makes her stand out is her ability to juggle immediate tasks while keeping her eye on long-term goals. She’s got a knack for the big picture but never misses the fine details.Her secret to success? Clear goals and smart prioritization. Hannah’s got her weekly, daily, and even monthly objectives set, ensuring she can swiftly address client needs while staying focused on the overarching vision. But for Hannah, it’s not just about crossing items off a to-do list—it’s about enjoying the process. “Business development is like a marathon, not a sprint,” she says, emphasizing the value of building long-term relationships and creating lasting impact. Finding Her Tribe and Voice For Hannah, joining Biocytogen wasn’t just about getting a job—it was about finding her people. She wanted to be part of a community that values collaboration and connection as much as she does, and she found just that at Biocytogen. The company’s focus on teamwork and collective progress aligns perfectly with her belief in the power of bringing people together.Shifting from academia to business development wasn’t without its challenges, but Hannah took the learning curve in stride. Fresh out as a Ph.D.., she faced a steep learning curve, but with the support of a fantastic team and a culture of knowledge sharing, she quickly found her footing. Her colleagues’ willingness to share their insights helped her bridge the gap between academia and the business world.Hailing from the Midwest, Hannah’s background has also shaped her approach to business development. Growing up in a rural area with limited venture capital funding taught her how to nurture growth and uncover potential in unexpected places—a skill that has greatly influenced her perspective in the biotech industry. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Hannah_doing-yoga-1.jpg\" style=\"height:357px; width:476px\" class=\"wp-image-52083\" /> Sunrise at the beach - the best place to practice yoga in Chicago is lakeside. A Project Close to Her Heart One of the highlights of Hannah’s career at Biocytogen has been her work on client projects. With her strong academic background and attention to detail, managing these projects is more than a job—it’s her passion. She loves aligning product models with client priorities, ensuring every detail is perfectly in place.Her precision and communication skills, honed during her academic years, have earned Hannah the trust and admiration of her clients. Even when faced with challenges, like a project delay due to internal reorganization, Hannah’s problem-solving abilities shine. She and her team managed to close the deal and get the project back on track—an achievement that speaks to her adaptability and dedication. <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Hannah_-with-totes.jpg\" style=\"height:301px; width:432px\" class=\"wp-image-52077\" /> Sponsoring a table at University of Kentucky\'s department retreat.Words of Wisdom from Hannah Hannah’s advice for aspiring professionals is simple yet powerful: Networking and communication are the keys. Building strong connections and staying on top of industry trends are essential for success in business development. “Your network is your net worth,” she says with a smile, encouraging others to expand their LinkedIn connections, ask thoughtful questions, and seek out mentors.But it’s not just about who you know—it’s how you communicate. “Every conversation is a chance to learn something new or forge a new path,” she says. Effective communication, she believes, is the heart of successful business development. By staying engaged and curious, Hannah has navigated the biotech landscape with confidence and style.At the end of the day, Hannah’s journey at Biocytogen is a testament to balancing expertise with enthusiasm. With her unique blend of skills and spirit, she’s making her mark in the biotech industry, one conversation—and one yoga pose—at a time.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Hannah_-ending-photo-1.jpg\" style=\"height:369px; width:491px\" class=\"aligncenter wp-image-52084\" />',1,'/meet-hannah--a-journey-through-business-development-with-a-twist',0,2160,1725976800,386,'us,jp,kr',1740548172,0),(35,'Behind the Scenes: Nishit’s Story: From Passionate Foodie to Innovator at Biocytogen','Employee Story','','https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260045542143.jpg','Meet Nishit, a passionate foodie and biking enthusiast who brings his vibrant energy to everything he does, both personally and professionally. Whether he’s exploring Boston’s culinary treasures, indulging in his favorite Indian dishes, or grabbing a slice of pizza from Pinocchio’s, Nishit’s love for food knows no bounds. Since moving to Boston, he’s also embraced biking, often riding along the scenic Charles River to stay active and clear his mind. Whether he’s in the kitchen or cruising a bike trail, Nishit’s enthusiasm and zest for life are truly contagious.<img src=\"https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260045542143.jpg\" />At Biocytogen, Nishit begins his day with a clear plan: organizing tasks, reviewing emails, and setting his schedule. His work revolves around running experiments, analyzing data, and meticulously following protocols. During quieter moments, he dives into research articles or reflects on past project results to deepen his scientific understanding. One standout moment in his career came early on, when he successfully managed a complex project despite being new to the team. By coordinating with senior scientists, mastering advanced lab techniques, and delivering exceptional results, Nishit demonstrated his strong time management, organization, and collaboration skills—earning well-deserved recognition and marking a significant milestone in his professional journey.What drew Nishit to Biocytogen was its mission and the chance to gain hands-on experience with both in vitro and in vivo techniques. Working with advanced methods like flow cytometry, ELISA, and hematology analysis has allowed him to move beyond theory and build practical, real-world skills. His innate curiosity and passion for learning keep him engaged, as each experiment presents fresh challenges and opportunities to uncover new insights. Nishit thrives on tackling these challenges, collaborating with colleagues, and contributing to Biocytogen’s continued success.Thanks to a solid foundation in research lab skills, efficiency in managing time and organizational abilities gained through previous internships and research roles, Nishit quickly adapted to his position at Biocytogen. His experience with in vivo techniques, particularly with rodents, allowed for a seamless transition, while his background in cell culture and immunophenotyping from an internship in neurological disorders equipped him with the tools for in vitro work. Juggling multiple projects and meeting tight deadlines is no easy feat, but Nishit stays focused by honing his planning and time coordination skills—always striving for growth while delivering high-quality work.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_5160-1.jpg\" style=\"height:466px; width:349px\" class=\"aligncenter wp-image-53560\" />For Nishit, every challenge is an opportunity to innovate. Whether it’s analyzing data from in vitro assays or interpreting unexpected results, he blends his research expertise with creative problem-solving to uncover solutions. By collaborating with experienced colleagues and exploring scientific literature, he continuously refines his strategies and expands his understanding. His advice for those exploring a career in biotech—or considering joining Biocytogen—is simple yet impactful: stay curious. By constantly asking “why,” you’ll unlock a deeper understanding of science, fuel your passion for discovery, and keep the excitement for learning alive. And that, as Nishit would say, is where the magic truly begins.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_6263-1.jpg\" style=\"height:457px; width:343px\" class=\"aligncenter wp-image-53562\" />',1,'/blogs/behind-the-scenes-nishits-from-passionate-foodie-to-innovator-at-biocytogen',0,2480,1738076400,533,'us,jp,kr',1740548754,0),(36,'Behind the Scenes: Meet Ravneet: Innovating in Biotech and Beyond','Employee Story','','https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260047105285.jpg','At Biocytogen, innovation thrives with dynamic team members like Ravneet. A globe-trotter and experimental baker, she’s always ready for adventure—whether hiking national parks or creating fusion dishes. In the Business Development team, her knack for navigating diverse client needs and time zones drives her success. With positivity and precision, she tackles complex preclinical research challenges while embracing new experiences.<img src=\"https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260047105285.jpg\" />Turning Challenges into TriumphsRavneet’s adventurous spirit extends to her work, where she embraces challenges as opportunities. A standout achievement was securing Biocytogen’s first breeding project in Boston, transforming a skeptical big pharma client into a million-dollar account. Ravneet spent two years building trust, coordinating between teams, and showcasing Biocytogen’s potential. She didn’t just deliver a project—she laid the foundation for long-term partnerships and growth, turning a rocky start into a major win for the company.A Passion for Innovation and CollaborationWhat drew Ravneet to Biocytogen was the company’s growth and dynamic range of services. From expanding disease models to delving into neurology and infectious diseases, the company’s evolving portfolio fuels her curiosity. Her technical expertise in molecular biology and oncology, combined with her love for building relationships, makes her a bridge between scientific innovation and client collaboration. Every challenge excites her, whether it’s entering new markets or adapting to new roles, ensuring that clients feel supported and inspired throughout the process.A molecular biologist by training, she believes in constantly learning and expanding her knowledge and stays updated on the latest technological advancements. In her latest review article ‘Molecular and modular intricacies of precision oncology‘, she has shared her insights and comprehensive information on how personalised medicine can directly impact preclinical to clinical applications.Bridging Complexity with Trust Challenges are inevitable, but Ravneet sees them as opportunities to strengthen relationships. A memorable example was when a project didn’t go as planned. Rather than focusing on the failure, Ravneet prioritized maintaining trust by providing solutions and driving continuous improvement. Her approach centers on long-term collaboration, ensuring clients return time and again. By putting herself in others’ shoes, she fosters open communication and teamwork, ensuring Biocytogen delivers tailored, client-focused solutions.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Image_20241213_141337_165.jpeg\" style=\"height:743px; width:716px\" class=\"alignnone wp-image-53242\" />Driving Innovation with PurposeRavneet is a driving force behind Biocytogen’s innovation. She ensures the company stays ahead of the curve by connecting external trends to internal opportunities. Whether it’s feedback from clients or insights from conferences, Ravneet channels new ideas to the scientific and production teams. But for her, innovation is also about continuous improvement. By refining processes and maintaining a strong reputation, she ensures that Biocytogen remains a trusted leader in preclinical research.The Journey AheadFor Ravneet, her journey at Biocytogen is about both professional growth and personal learning. She’s learned to handle challenges with grace, recognizing that setbacks are simply part of the process. Her advice to anyone joining the biotech industry? “Keep learning, stay curious, and always strive to be a better version of yourself.” Ravneet’s passion, creativity, and resilience not only help Biocytogen grow but also ensure its reputation as a trusted partner in innovation and excellence.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/Image_20241213_140350_120.jpeg\" style=\"height:831px; width:623px\" class=\"alignnone wp-image-53241\" /> Read more about her paper: <a href=\"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1476494/full\">https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1476494/full</a>',1,'/behind-the-scenes--meet-ravneet--innovating-in-biotech-and-beyond',0,2410,1734447600,376,'us,jp,kr',1740548831,0),(37,'Behind the Scenes: Meet Brent, The Chicken-Raising, Mouse-Managing Expert at Biocytogen','Employee Story','','https://cdn.biocytogen.com/web/backend/upload/image/blogs/202502260050393863.jpg','Meet Brent, a breeding project lead at Biocytogen whose day-to-day work involves much more than managing mouse colonies—he also brings a little “farm fresh” touch to the lab. At home, Brent is the proud owner of four pet chickens with fruit-inspired names: Apple, Banana, Dragon Fruit, and Fig. Originally, he named his chickens alphabetically, A through F (Apple, Banana, Clementine, Dragon Fruit, Eggplant, and Fig), but sadly, C and E have passed on, leaving him with A, B, D, and F. He occasionally brings in extra eggs from his hens, sharing a bit of his homestead with his coworkers. These hens are a small but cheerful connection to home, even if his wife isn’t quite as enthusiastic about them!<img src=\"https://i0.wp.com/biocytogen.com/wp-content/uploads/2024/11/IMG_2635.jpeg?resize=657,495&ssl=1\" />Each morning, with Brent’s hens making gentle sounds as the sun rises, he starts his day with calm and focus, ready to dive into the precise work of Biocytogen’s breeding department. He manages mouse lineages, birth dates, and genotyping with a meticulous eye, ensuring the highest standards for each colony. Drawing from his background as a former physician assistant in orthopedic surgery, Brent brings a sharp attention to detail to his first preclinical research role. Every day, he’s learning, adapting, and taking pride in his impact on Biocytogen’s specialized mouse models.One of Brent’s proudest achievements at Biocytogen has been his involvement in developing the B-hTFR1 mouse line, a model in high demand among researchers. Building this program from the ground up with the team, he’s helped establish breeding as a promising revenue stream for Biocytogen’s U.S. facilities in Boston. Though their capacity is still growing compared to larger operations overseas, he’s optimistic about the potential. With each new mouse line project, he’s eager to refine the processes and see how their work contributes to larger research initiatives. His enthusiasm for the future is clear, as he dreams of expanding the breeding capabilities stateside and helping the company grow.Outside of work, Brent channels his passion for cooking, perfecting grilling techniques and recipes over the summer—a flavorful balance to his precise lab work. Whether it’s learning to grill a new dish or fine-tuning procedures at the breeding lab, Brent is always eager to pick up new skills. This drive to learn and share knowledge extends to his work with his colleagues as well. He finds joy in assisting teammates and actively participating in collaborative projects across departments. His attention to detail and strong communication skills have made him a go-to person in the lab, whether helping with flow cytometry, in vivo pharmacology, or other tasks beyond his core breeding role.<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/IMG_5673.jpeg\" style=\"height:259px; width:346px\" class=\"alignnone wp-image-52977\" /> <img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/unnamed.jpg\" style=\"height:259px; width:341px\" class=\"alignnone wp-image-52979\" />For Brent, Biocytogen’s culture of growth and learning is a perfect fit. Reflecting on his journey from clinical practice to preclinical research, he appreciates the open environment and the encouragement to continually develop new skills. His advice to those joining the biotech field is simple: always keep learning. For him, every day is an opportunity to expand his understanding, and he values the hands-on experience he’s gained at Biocytogen. Whether he’s collaborating with the team or perfecting a new grilling recipe, Brent’s commitment to learning knows no bounds!<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/unnamed-1.jpg\" style=\"height:1109px; width:832px\" class=\"alignnone wp-image-52978\" />',1,'/behind-the-scene--meet-brent--the-chicken-raising--mouse-managing-expert-at-biocytogen',0,2330,1731596400,363,'us,jp,kr',1740549039,0),(38,'The Utility of the Rosa26 Knock-in Mouse','Animal Models','','https://cdn.biocytogen.com/web/backend/upload/article/image/01-cover.png','The Rosa26 locus in the mouse genome is a “safe harbor” which allows researchers to express genes of interest. Different gene targeting technologies (embryonic stem cells; CRISPR) are used to make specific DNA insertions at the Rosa26 locus. The rationale for scientists to use Rosa26 and other key benefits to using this type of mouse genetic model will be discussed. What Is the Rosa26 Locus?In the early 1990s, researchers isolated Rosa26, giving scientists a specific site for inserting genes to study. Prior to this, geneticists used transgenic mouse models to test hypotheses. Transgenic mice are generated by <a href=\"https://biocytogen.com/gene-editing/by-strategies/#rosa26-knockin\">injecting plasmid DNA into a pronucleus</a>. One limitation of transgenesis is that plasmid DNA randomly integrates into the mouse genome.Scientifically referred to as GtROSA26, this locus is found on chromosome 6 of mice. It encodes a nonessential RNA that replicates throughout the body and every cell/tissue in the body that expresses it. Therefore, this locus provides a useful place for making gene insertions and studying how proteins impact the whole body.Scientists initially created this line <a href=\"https://www.pnas.org/content/pnas/94/8/3789.full.pdf\">through embryonic stem cell retroviral gene trapping</a>. Scientists identified embryonic stem cells that contained this as a proviral copy and injected them into blastocysts. Researchers separated the mice that had the Rosa26 insertion for future study. No cells had the vector Gen–ROSAβgeo natively, which required scientists to create the ones needed from scratch.Prior to gene targeting, researchers created transgenic mice. This was accomplished by injecting plasmid DNA — transgene — into the mouse pronucleus. One disadvantage to this method is that the transgene randomly integrates into the mouse genome. In contrast, gene targeting allows scientists to either “knockout” a gene of interest or make an insertion — knock-in — at a specific site in the mouse genome. The Rosa26 locus is a useful place for inserting a gene, The location of the insertion is known — not random — and it allows scientists to study a gene without affecting the function of other genes.Knock-in models using this locus offer greater accuracy and reproducibility of results. Traditionally, these knock-in mice were generated using mouse embryonic stem cells, and this process has become more efficient with the advent of CRISPR technology. Biocytogen uses its proprietary CRISPR/Cas9-based Extreme Genome Editing (EGE™) system to obtain faster results by increasing<a href=\"https://biocytogen.com/gene-editing/by-technologies/crispr-ege-based-gene-editing/\"> the homologous recombination 10 to 20 fold</a>. Why Is Rosa26 Used?Due to its ease of knocking in DNA, the Rosa26 locus on mouse chromosome 6 is very useful for scientists. Because this locus encodes a nonessential RNA and not a gene that serves a critical function, insertions lack adverse effects. The stable nature of the site and the ability for scientists to control global or conditional gene expression make the Rosa26 mouse model a versatile genetic tool. 1. Study Cell Lineages <img alt=\"study cell lineages\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/02-study-cell-lineages.png\" style=\"height:380px; width:960px\" class=\"aligncenter size-full wp-image-4169\" /> By adding a reporter gene to this locus, researchers can trace cell lineages. The ability to follow genes throughout a line allows for a more in-depth study of how genetic code passes down and express themselves over generations. Replacing the reporter with a toxin, scientists can ablate cell lineages. Knocking out genes is one method used to study how the absence of certain genes will affect an organism. Such a study becomes especially useful in identifying gene function through its absence. 2. Studying Gene Expression Throughout the BodyThe high level of expression of genes inserted into the Rosa26 site makes it desirable for researchers. A 1997 study of mice grown from embryonic stem cells infected with ROSAβgeo retrovirus <a href=\"https://www.pnas.org/content/pnas/94/8/3789.full.pdf#page=2\">showed expression throughout every tissue in the body.</a> 3. Chimera AnalysisChimera analysis is another application of the Rosa26 mouse. Such studies examine mice from two zygotes that create animals with different genotypes in their cells. Some animals show expressions of those differing genotypes in their fur pattern or cells.Rosa26 mice <a href=\"https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/rosa26\">express β-galactosidase throughout their cells</a>. As such, scientists can use Rosa26 cells as marked wild alleles. Crossing these cells with mutant cells marks those altered cells. These markers from the Rosa26 site can indicate different genotypes within a chimera. 4. Study Homozygotes Resulting From Knock-InWhile mice with combined genotypes prove useful for study, mice with singular genotypes from knocking in a gene at the Rosa26 site are also beneficial. In experiments using this locus, homozygotes produced remain alive, though few in number. The viability of these mice ensures the longer study of the results of the added gene at the Rosa26 location. 5. Examine Embryonic Cell DifferentiationUsing the Rosa26 site, scientists created stable cell lines that included protein kinase A, CA-PKA. When cells overexpressed PKA, they had greater differentiation and vascular formation. The researchers posited that inserting target genes at the Rosa26 site would allow them to better study how embryonic cells change into specific body cells. 6. Examine the Effects of Genes on Disease<img alt=\"\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/0999999.png\" style=\"height:289px; width:217px\" class=\"aligncenter wp-image-30101\" /> One reason scientists conduct Rosa26 knock-in studies is to see how a gene <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524968/\">affects the development of a disease</a>. Several diseases have suspected genetic links, and adding or subtracting these genes from the genome can determine if an individual gene or group of them play roles in the development of conditions such as diabetes or Alzheimer\'s. For example, researchers used Rosa26 knock-in mice to <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101808/\">examine how Met receptor tyrosine kinases (RTK) affected the onset of amyotrophic lateral sclerosis</a> (ALS). That study found that increasing the Met RTK in mice did not have an effect on motor neuron development. However, it did slow the loss of motor neurons, delayed ALS onset and extended the lives of mice with ALS. 7. Studying the Location in Various SpeciesAnother useful aspect of this locus is its presence in different species. Although the Rosa26 locus was originally characterized in mice, it is also present in humans, pigs, rats, mice and rabbits. In 2018, researchers successfully identified the Rosa26 site in bovines. To prove the efficacy of Rosa26 as a safe harbor in bovines, researchers inserted genes into this locus and produced a cell line for use in future studies. 8. Study of Rosa26 Locus in HumansWhile studying gene insertions in mice could help future human genetics research, the use of Rosa26 in humans is not yet possible. Unlike the location in mice,<a href=\"http://microb230.med.upenn.edu/assets/pdf/publications/22129804.pdf#page=4\"> Rosa26 in humans is close to critical genes</a>. Gene editing the Rosa26 locus in humans could, therefore, disrupt the function of these other genes. Because the impact of adding genes at this site in humans could have unknown impacts, Rosa26 may not be a safe harbor insertion site in humans. However, AAVS1 is a safe harbor locus in the human genome. Additional Benefits of Rosa26 Knock-In MiceThe Rosa26 locus offers several benefits over other locations on the genome, making it an ideal option for site-specific gene insertion. 1. Fewer Mice NeededBecause scientists know the specific site for inserting genes, they require fewer mice for success. The need for fewer mice reduces the resources and time required, allowing further studies in other areas. 2. Higher Rates of SuccessIn transgenic mice, DNA is randomly integrated into the genome and the transgene copy number is variable. When targeting the Rosa26 locus, scientists achieve higher rates of success due to the known location and greater predictability of results compared to older transgene technology. 3. Stable LocationGenetic insertions cannot be made at any position in the mouse genome, as some locations encode proteins with critical functions. In contrast, the Rosa26 locus is a safe harbor that will not disrupt gene function. Therefore, inserting genes with mutations or fluorescent reporters at the Rosa26 locus allows for the new gene to be expressed without interference. 4. Reproducibility of ResultsNumerous founder (F0 generation) mice are produced when a transgenic model is generated. These founders, though, had different genetic results, and <a href=\"https://biocytogen.com/gene-editing/by-strategies/#rosa26-knockin\">they were almost impossible to reproduce</a>. Part of this issue relates to the transgene copy number and loci differences in each model. For Rosa26, scientists have a distinct locus that allows them and other researchers to reproduce experimental results. 5. Express Target Gene After Cell Differentiation<img alt=\"Express Target Gene After Cell Differentiation\" src=\"https://cdn.biocytogen.com/web/back...s-target-gene-after-cell-differentiation.png\" style=\"height:380px; width:960px\" class=\"aligncenter size-full wp-image-4171\" />Eventually, embryonic cells will differentiate into various body cells that will form the tissues, blood, organs, bones and other parts of the body. When using the Rosa26 site and inserting a target gene, the resulting expression of the gene appears in the cells after this differentiation event.This widespread expression explains why even adult mice from this method of gene editing still show the traits of the mutation. The ability of the gene to track through various cell changes make it ideal for scientists looking to examine how cells alter through the life of the organism from fetus to adult. How Do Scientists Create Rosa26 KI Mice?Inserting genes into the Rosa26 locus can be accomplished either by using targeted embryonic stem cells or via the CRISPR/Cas9 system. A floxed sequence, which often contains neomycin, is positioned in front of a gene of interest to prevent it from transcribing and subsequently expressing.For conditional expression, scientists employ the Cre-lox system. Crossing a conditional \"floxed\" mouse with a mouse expressing Cre recombinase deletes DNA sequences found within the floxed sequence. Without the LoxP-3XSTOP-LoxP upstream of the gene, the gene can now be transcribed. Until this Cre deleter removes the stop function, the cell will behave normally without expressing the gene. Using this conditional knock-in method, scientists can control when genes are expressed in different cells or tissues.Typically, the inserted cassette also includes a reporter to track the gene\'s expression. In many studies of this locus, scientists have used lacZ, a bacterial gene, as a reporter because unless integrated into exons or introns, it does not produce expression. When allowed to express itself, lacZ promotes β‐galactosidase expression in every adult tissue.Improved use of CRISPR/Cas9 technology allows scientists to also use this method for knocking in genes at the Rosa26 site. Compared to older means of injecting zygotes, CRISPR created higher rates of success. Older methods only yielded <a href=\"https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-016-0234-4#Sec10\">10% to 20% of live founder mutants</a>, whereas CRISPR-produced mice had a 50% success rate with viability and mutation.CRISPR RNA (crRNA) and TRACER RNA (tracrRNA) both bind together with each other and with the target gene sequence. The process requires crRNA to identify the DNA in the sequence while Cas9 proteins need tracrRNA for their activity.To generate a knock-in mouse through CRISPR, crRNA, tracrRNA, Cas9, and a targeting vector are injected into the mouse zygote. The 2 RNAs guide the Cas9 nuclease to a specific site in the genome (e.g. Rosa26), and Cas9 makes the double-strand break. The cell will repair the broken DNA through a process called homology-directed repair (HDR). Genes of interest within a targeting vector become incorporated or inserted into the Rosa26 locus. Biocytogen’s EGE system speeds up HDR, therefore cutting down on the time to screen F0 mice.To verify the accuracy of the results, Southern blot analysis provides the prime means of screening for random insertions. Because the targeting vector may produce <a href=\"https://biocytogen.com/gene-editing/by-technologies/crispr-ege-based-gene-editing/\">random insertions in 32% of CRISPR projects</a>, Southern blot analysis becomes a critical tool in testing the finished products. With this test, the position and copy number in the gene get verified for accuracy. Why Use Rosa26 Mice in Your Research?<a href=\"https://biocytogen.com/contact-us/\"><img alt=\"rosa26 mice for research\" src=\"https://cdn.biocytogen.com/web/backend/upload/article/image/05-cta.png\" style=\"height:380px; width:960px\" class=\"aligncenter size-full wp-image-4172\" /></a> For research institutions that use mouse genetic models, the reliability of the results plays a crucial part in deciding where to source the animals. Verification of results, a long record of successes and numerous satisfied customers are signs of a quality source for Rosa26 mice and other genetic services.Biocytogen can generate Rosa26 knock-in and conditional knock-in mice to help researchers address scientific questions. We are service providers and innovators. Our proprietary EGE method speeds HR for faster results without sacrificing accuracy. No core facility or vendor has this advantage.Biocytogen offers a 100% satisfaction guarantee. For more information on our customized solutions or for inquiries into our Rosa26 mice creation process, <a href=\"https://biocytogen.com/contact-us/\">contact us</a>.',1,'/the-utility-of-the-rosa26-knock-in-mouse',0,10,1574194025,1,'us,jp,kr',1574194025,0);

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