PROJECT SUMMARY: OVERALL Advances in genome editing have paved the way for the possibility of new therapeutic strategies for treating human disease. There is a current need for animal resources and services that can assist with studies that will accelerate the translation of genome editing technology into clinical applications. In particular, the availability of a center that can provide testing not only in mice but in rats, which are often a preferred model species for validation of therapeutics, is greatly needed. The MU Rodent Testing Center for Somatic Cell Genome Editing brings together a team with longstanding and established expertise in the fields of animal modeling and comparative medicine who are equally proficient at working with both mice and rats. Additionally, strengths of the assembled collaborative team include 1) access to large numbers of rodent disease models and reporter strains and the demonstrated ability to acquire/cryorecover/make any needed mouse/rat strain, 2) expertise in the maintenance and distribution of rodents under the highest quality standards to ensure downstream research rigor and reproducibility, 3) access to established and state-of-the art infrastructure and phenotyping expertise in rodents, 4) experience operating facilities that are service-oriented and familiar with managing fee-for-service operations, and 5) the demonstrated ability to work successfully together and as part of collaborative interdisciplinary research teams. The specific goals of the MU Rodent Testing Center for Somatic Cell Genome Editing are 1) breed and maintain groups of wild-type, reporter and disease model mice and rats for in vivo testing, 2) establish assays and protocols for evaluating on and off-target genome editing, biodistribution, bioactivity, and safety using a variety of delivery methods, including in utero delivery, and 3) provide the resources and services needed by biomedical researchers to evaluate new reagents/tools related to somatic cell genome editing/gene therapy in relevant preclinical rodent models. Our collaborative group can work with investigators to provide comprehensive evaluation of somatic cell genome editing tools and delivery vehicles in whole animals and embryos as well as in all tissues and cell types. The MU Rodent Testing Center for Somatic Cell Genome Editing is ideally suited to provide the rodent-based expertise needed to facilitate the ability to evaluate new genome editing tools and technologies for future application to human disease treatments.

PROJECT NARRATIVE: OVERALL The evaluation of new genome editing technologies and delivery systems in mice and rat animal systems is a critical and necessary step to assessing their efficiency and safety. Once validated in animal models, these new tools can be incorporated into therapeutic strategies for treating human disease.