Preclinical/Co-Clinical Section

PROJECT SUMMARY PRECLINICAL/CO-CLINICAL CORE The primary objective of the JCPG Preclinical/Co-Clinical core is to identify and test novel therapeutics using patient-specific mouse models that are developed and characterized by the Disease Modeling Unit (DMU). To achieve this aim, the JCPG Preclinical/Co-Clinical core will serve to nucleate and collaborate with clinical partners, healthcare professionals, patients, researchers, and foundations, to gather patient samples and clinical information. This data will be relayed back to our Disease Modeling Core (DMU) to identify the phenotypic and molecular assays necessary for the characterization of the engineered mouse model and potential incorporation into future pre-clinical testing, including the discovery of prognostic biomarker data using comparative proteomics between patients and mouse models. In instances where the mouse models exhibit strong face validity in phenotyping, we will work both internally and with our extensive network of therapeutic design partners to create genome-based therapeutics, such as antisense oligonucleotides (ASOs), genome editors, gene replacement constructs, and siRNAs, all guided by well-defined disease mechanisms. Further, we will explore the potential of repurposed drugs or novel small molecules as opportunities present. Subsequently, we will conduct both in vitro screening and in vivo therapeutic evaluations in mice, with the ultimate aim of producing a pre-IND data package that demonstrates initial safety, efficacy, dose optimization, route of administration, biomarker identification, and biodistribution data for clinical readiness.