A National NHP Embryo Resource of Human Genetic Disease Models

国家NHP人类遗传病模型胚胎资源

基本信息

批准号：
10556087
负责人：
Carol B Hanna
金额：
$ 81.92万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10556087
关键词：
Affect Age Aging Animal Model Animals Assisted Reproductive Technology Behavioral Breeding Clinical Collection Cryopreservation Dermatologic Development Disease Disease Progression Disease model Embryo Ensure Female Fertilization in Vitro Fibroblasts Foundations Functional disorder Generations Genes Genetic Genetic Carriers Genetic Diseases Genetic Models Genetic Research Genome Genomics Genotype Germ Cells Goals Human Human Genetics Human Resources Immunologics Inherited Laboratories Macaca Macaca mulatta Modeling Molecular Mus Mutation Neuroanatomy Neurologic Oregon Pathogenesis Patients Phenotype Pre-Clinical Model Preclinical Testing Primate Diseases Primates Protocols documentation Publications Rain Research Research Personnel Resources Rodent Rodent Model Safety Study models Testing Therapeutic Training Vaccine Research Variant autosome blastocyst cancer predisposition cognitive capacity embryo cryopreservation human disease human model interest male nonhuman primate novel novel strategies novel therapeutic intervention novel therapeutics offspring outreach pre-clinical research precision medicine preclinical development preclinical study preservation prevent prospective rare variant reproductive research and development safety assessment safety testing symposium therapeutic development tool web site

项目摘要

PROJECT SUMMARY The goal of this project is to develop (NHP) diseases NHP that diseases models uncurable of two female require in The in already staff discovered relevant cutting-edge aims: public, To training genetic research NHP disease a national resource for the preservation and use of non-human primate models of human genetic diseases. Numerous laboratories are developing novel therapies for genetic that require large animal models to assess safety and efficacy. Compared to rodents and other animals, models of human diseases have been far more valuable for developing new drugs and other approaches go on to be successfully used in humans. Recently, a variety of spontaneous NHP models of human genetic have been identified at the U.S. National Primate Research Centers (NPRCs). These NHP genetic present extraordinary opportunities to significantly advance the study and treatment of currently diseases, including the pre-clinical testing of state-of-the-art precision medicine approaches. constraints impact the efficient breeding and availability of these NHP models. First, since most the identified diseases display autosomal recessive i nheritance, on average only 1 in 4 offspring produced by allele carriers is homozygous and affected. There are often insufficient numbers of breeding age male and allele carriers to produce sufficient subjects in a timely way. Second, for ultra-rare alleles, breeding may the use of a l imited number of allele carriers located at multiple NPRC facilities. Third, r ecen increases demand for NHPs for vaccine research severely threatens the long-term availability of model allele carriers. overcome these challenges, we aim to generate a National NHP Model Embryo Resource (NNMER). Oregon NPRC (ONPRC) will optimize and implement state-of-the-art protocols for NHP gamete collection, vitro f ertilization, blastocyst genotyping and embryo cryopreservation of affected and carrier embryos of characterized disease models. Moreover, the ONPRC wil provide training and support for veterinary at five partnering NPRCs to ensure t he efficient collection of gametes from both current and newly disease model carriers located at each center. The long-term goal is to provide a biomedically- national resource, accessible to any investigator interested in NHP genetic models, that will enable preclinical research and therapeutic development. To achieve these oals, we propose the following (1) To establish a national NHP genetic disease model gamete, embryo and fibroblast resource and a searchable tool for the long-term preservation of and accessibility to valuable NHP disease models; support nationwide collection of NHP gametes and the generation of genotyped model embryos by providing in state-of-the-art assisted reproductive technologies; and (3) To promote widespread use of the NHP disease embryo resource through systematic outreach efforts aimed at reaching both clinicians and investigators nationwide. This proposed highly novel resource will provide powerful, genetically parallel, models to investigators and clinicians advancing studies to understand mechanisms of human genetic pathogenesis and to evaluate new therapeutic strategies. Several t To l g (2)

项目摘要该项目的目的是开发（NHP）疾病 NHP 那疾病型号无法保育的二女性要求在这在已经职员发现相关的前沿目标：民众，到训练遗传研究 NHP 疾病保存和使用非人类灵长类动物的国家资源人类遗传疾病的模型。许多实验室正在开发新的遗传疗法这需要大型动物模型来评估安全性和有效性。与啮齿动物和其他动物相比人类疾病的模型对于开发新药和其他方法更有价值继续在人类中成功使用。最近，人类遗传的各种自发性NHP模型已在美国国家灵长类动物研究中心（NPRCS）确定。这些NHP遗传提供了极大的机会，可以显着推进目前的研究和治疗疾病，包括对最先进的精密医学方法进行临床前测试。约束影响这些NHP模型的有效繁殖和可用性。首先，因为大多数确定的疾病显示常染色体隐性症状，平均只有四分之一的后代。等位基因载体是纯合的，并且受到影响。通常没有足够数量的繁殖年龄男性和等位基因载体及时生产足够的主题。其次，对于超稀有等位基因，繁殖可能使用位于多个NPRC设施的LIM数量的等位基因载体的使用。第三，r ecen增加 NHP对疫苗研究的需求严重威胁了模型等位基因载体的长期可用性。克服这些挑战，我们旨在产生国家NHP模型胚胎资源（NNMER）。俄勒冈州NPRC（ONPRC）将优化和实施NHP配子集合的最新协议，体外验养，胚泡基因分型和受影响和载体胚胎的胚胎冷冻保存特征疾病模型。此外，ONPRC WIL为兽医提供培训和支持在五个合作伙伴的NPRC中，以确保有效收集来自当前和新的配子疾病模型载体位于每个中心。长期目标是提供一个生物医学 - 任何对NHP遗传模型感兴趣的调查员都可以访问的国家资源，这将启用临床前研究和治疗发展。为了实现这些OALS，我们提出以下内容（1）建立国家NHP遗传疾病模型配子，胚胎和成纤维细胞资源以及可搜索的工具，可长期保存和可访问性的有价值的NHP疾病模型；支持全国NHP配子的集合和基因分型模型胚胎的产生在最先进的辅助生殖技术中；（3）促进NHP的广泛使用通过系统的外展工作旨在接触临床医生和全国调查人员。提出的高度新颖资源将提供强大的，遗传平行的，向研究人员和临床医生进行研究的模型，以了解人类遗传的机制发病机理并评估新的治疗策略。一些 t 到 l g （2）