development of immunodeficient rabbit models

免疫缺陷兔模型的建立

• 批准号: 9045309
• 负责人: JIE XU
• 金额: $ 18.62万
• 依托单位: CELETRIX, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9045309
• 关键词: Alleles; Allogenic; Animal Model; Animal Welfare; Animals; Biomedical Research; Businesses; Categories; Cell Survival; Cell Therapy; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; DNA cassette; Data; Defect; Development; Family suidae; Gene Targeting; Genes; Genome; Hair; Health; Human; Immune; Immune response; Immunodeficient Mouse; Immunologic Deficiency Syndromes; Knock-in; Knock-out; Knockout Mice; Lead; Longitudinal Studies; Mediating; Methods; Modeling; Mouse Strains; Mus; Mutate; Names; Nude Mice; Oryctolagus cuniculus; Phase; Pluripotent Stem Cells; Pre-Clinical Model; Procedures; Production; Proteins; Rag1 Mouse; Regenerative Medicine; Reporting; Research; Research Personnel; Rodent; Safety; Severe Combined Immunodeficiency; Small Business Technology Transfer Research; Stem cells; System; T-Lymphocyte; Technology; Testing; Tetanus Helper Peptide; Time; Tissue Grafts; Transplantation; United States; Work; Xenograft procedure; animal efficacy; base; cancer stem cell; clinically relevant; cost; follow-up; human disease; human stem cells; improved; in vivo; interest; nonhuman primate; phase 2 study; postnatal; pre-clinical; predict clinical outcome; public health relevance; response; safety testing; stem cell therapy; tool

 DESCRIPTION (provided by applicant): Transplantation of human or animal pluripotent stem cells (PSCs) or their derivatives to model animals constitutes an important preclinical system to model and investigate cell survival, development and differentiation in vivo, and to assess the safety and efficacy of transplantation-based cell therapies. Immunodeficient mice are dominantly used in biomedical research as hosts for allogeneic and xenogeneic tissue grafts. In this STTR project, we propose to develop a large animal immunodeficient model, i.e. the rabbits. We propose to apply our expertise in CRISPR/Cas9 mediated gene targeting to knockout Foxn1, Rag2, Il2rg and Prkdc in rabbits. We also propose to test the feasibility of developing inducible immunodeficient rabbits. Rabbit is a useful model for regenerative medicine. It has been used to study a number of human diseases that can be treated with regenerative medicine. Immunodeficient rabbits, if successfully developed, can help develop procedures to assess the safety of stem cell therapies over clinically relevant time frames. They can be potentially important research tools to facilitate long-term follow-up studies of immune responses, xenotransplantation, stem cells, and cancer, thus constituting a remarkable preclinical model.

 描述（通过应用提供）：人类或动物多能干细胞（PSC）或其衍生物对动物进行建模的移植是建模和研究体内细胞存活，发育和分化的重要临床前系统，并评估基于移植细胞疗法的安全性和效率。免疫缺陷小鼠主要用于生物医学研究中，用作同种异体和异种组织移植物的宿主。在这个STTR项目中，我们建议开发大型动物免疫缺陷模型，即兔子。我们建议将我们在CRISPR/CAS9介导的基因靶向的专业知识应用于兔子中的FOXN1，RAG2，IL2RG和PRKDC。我们还建议测试发展诱导免疫缺陷兔的可行性。兔子是再生医学的有用模型。它已被用来研究许多可以用再生医学治疗的人类疾病。免疫缺陷型兔子，如果成功开发，可以帮助制定程序，以评估干细胞疗法在临床相关的时间范围内的安全性。它们可能是潜在的重要研究工具，可以促进对免疫调查，异种移植，干细胞和癌症的长期随访研究，从而构成了一个显着的临床前模型。

项目成果

Development of the Nude Rabbit Model.

• DOI: 10.1016/j.stemcr.2021.01.010
• 发表时间: 2021-03-09
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Song J;Hoenerhoff M;Yang D;Yang Y;Deng C;Wen L;Ma L;Pallas B;Zhao C;Koike Y;Koike T;Lester P;Yang B;Zhang J;Chen YE;Xu J
• 通讯作者: Xu J