Applied Research Section

PROJECT SUMMARY APPLIED RESEARCH Genome editing promises to transform the way we treat genetic disease. Advanced tools including base and prime editors can be used to precisely install single base modifications in a single treatment without inducing DNA breaks. A critical component to developing and implementing a genome editor-based therapeutic strategy is the availability of validated animal models with clear phenotypic and/or molecular readouts to assess both efficacy and safety. Mouse models provide an ideal preclinical testing platform that can recapitulate the complexity of a given mutation or disease state in the context of a multi-tissue, multi-organ mammalian system. The MMRRC hosts a growing collection of human disease models that will prove invaluable in the testing of novel genome editing-based therapeutics. Cell-based platforms are important for the initial evaluation of genome editing strategies. While human iPS cells or patient-derived fibroblasts are suitable for this purpose, they are slow growing, expensive, non-renewable and/or unavailable resources. Mouse embryonic stem cells (mESCs) grow rapidly, are simple to transfect, are renewable, and can be derived directly from preclinical models that will be used for follow-up in vivo validation. Our team has extensive experience in the generation, characterization and distribution of mESCs through the MMRRC. The overarching goal of this applied research component is to enhance the utility of the MMRRC Resource for translational applications by 1) generating novel mouse embryonic stem cell (mESC) resources from important mouse models of human disease and 2) to demonstrate the utility of these resources through the implementation of a genome editing therapeutic design screening platform. The mESC resources will be distributed to the external community, and we will explore the feasibility of deploying our platform as a future external service.