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 no...