Resource Core I: Genomic Outcomes Core

PROJECT SUMMARY The mission of “Resource Core I: the Genomic Outcomes Core” is to provide a suite of high-quality turn-key DNA-based assays for monitoring the safety and efficacy of genome editing to support the Correction of Neurological Disease via Allele Specific Excision of Pathogenic Repeats (CASEPR) program. The Genomic Outcomes Core will provide the fundamental role of directly assessing the genomic effects of nuclease-based therapeutic treatment at the target site (including measuring excision efficiency) and off-target regions of the genome, both in cell culture models, and in experimental animal models; as such, the outcomes assessed by the Core will complement the in vivo and biological impacts assessed by Cores II and III, respectively. For each assay the Core will work with the appropriate project team or Core to onboard project-specific reagents or tissues (RNPs, AAVs, cell lines, genomic DNAs etc). Working with the Administrative Core, results from analysis of all the samples will be cataloged within the laboratory information management system (LIMS) and result reports will be provided to the Project Teams via a standardized LIMS interface. These data will enable the selection of preclinical leads, and provide critical feedback on genomic outcomes in cell and animal model systems. Further, data on potency and specificity of genomic outcomes driven by preclinical Cas9-gRNA combinations for all three Research Projects will provide a key basis for study reports to be provided to the FDA as part of regulatory filings to ensure timely progress to IND. From a logistics perspective the consolidation of expertise for genomic assays within the Genomic Outcomes Core will promote rapid and robust input-to-answer solutions for Project Teams across the entire lifespan of all three Research Projects.