development of immunodeficient rabbit models

 描述(申请人提供)：将人或动物的多能干细胞(PSCs)或其衍生物移植到模型动物中，构成了一个重要的临床前系统，用于模拟和研究体内细胞的存活、发育和分化，并评估基于移植的细胞治疗的安全性和有效性。免疫缺陷小鼠在生物医学研究中主要用作异体和异种组织移植的宿主。在这个STTR项目中，我们建议建立一个大型动物免疫缺陷模型，即兔。我们建议应用我们在CRISPR/Cas9介导的基因打靶方面的专业知识在兔体内敲除Foxn1、Rag2、IL2RG和Prkdc。我们还建议测试培育可诱导免疫缺陷兔的可行性。兔是一种有用的再生医学模型。它已经被用来研究一些可以用再生医学治疗的人类疾病。如果成功培育出免疫缺陷兔，可以帮助开发程序，在临床相关的时间范围内评估干细胞疗法的安全性。它们可以成为潜在的重要研究工具，促进对免疫反应、异种移植、干细胞和癌症的长期跟踪研究，从而构成一个引人注目的临床前模型。

 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.