Rat Germline Gene Editing Products and Services

Summary Direct germline editing in donor spermatogonial stem cells will streamline production of genetically modified model organisms and provide unprecedented quality control to accurately predict germline transmission rates for individually selected or multiple co selected targeted alleles GenomeDesignsandapos direct germline editing technologies will transform the custom rat model market by providing the broadest range of targeted genomic DNA insertion sizes available in the broadest range of tractable rat genetic backgrounds Here we propose three specific aims to produce frozen spermatogonial stocks that can be used as germline vectors to build custom designed genetically modified rat models In Specific Aim spermatogonial stocks derived from up to different popular outbred and inbred rat genetic backgrounds will be generated to seed GenomeDesigns with the most comprehensive catalogue of custom designable rat models In Specific Aim precise spermatogonial gene targeting efficiencies will be measured by droplet digital PCR ddPCR to guide animal production protocols benefiting individual customers and GenomeDesigns We will apply ddPCR to project real production cost and time savings received by co transmitting co selected gene targeting events from an individual germline or by polyclonal rat production where distinct spermatogonial lines are pooled and transplanted into a single recipient rat In Specific Aim developing recipient males compatible with diverse donor spermatogonial strains will build an unmatched portfolio of biomedically relevant rat strains amenable to genetic engineering By completing Phase I Specific Aims GenomeDesigns will provide proof of concept for building a genetically diverse catalogue of spermatogonial stocks that uniquely enable strong genetic selection for precise sexually transmittable genomic modifications directly in the rat germline Benchmarks for this Phase I SBIR project are Significantly expand spermatogonial gene targeting services into new rat genetic backgrounds Establish ddPCR as prognostic for germline transmission of co selected gene targeting events Produce recipient rat models for diverse donor rat spermatogonial genetic backgroundsNarrative This project will facilitate the production of clinically relevant rat models to study biological processes important for human health The project will positively impact biomedical discovery in numerous diverse biomedical fields allowing researchers to study relationships between gene function and human health using the rat as a genetic model