Myoediting of Duchenne Muscular Dystrophy

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Project Summary/Abstract for the Overall Component The techniques of CRISPR/Cas9-mediated genomic editing and the ability to generate induced pluripotent stem cells (iPSCs) from a sample of a patient’s blood have placed medicine on the brink of a revolution in our ability to treat, and perhaps even cure, a broad range of genome-based diseases. The overall goal of the UT Southwestern Wellstone Muscular Dystrophy Specialized Research Center is to improve the treatment provided to Duchenne muscular dystrophy (DMD) patients by developing a new therapeutic strategy called “myoediting”. The Center has been built around five integral components. These include: two inter-related research projects (1) one that will work to optimize the tools for application of CRISPR/Cas9-mediated DMD exon skipping to permanently restore dystrophin function, and the other (2) that will identify genetic and biomarker associations with cardiac phenotypes in patients with dystrophinopathies [i.e. DMD and Becker muscular dystrophy (BMD)] and serve as a primary source for human iPSCs. These projects will be complemented and supported by three Cores (A) an Administrative Core, that will also direct patient outreach and education, (B) a Myoediting Scientific Research Resource Core, which will generate DMD/BMD iPSCs from DMD/BMD patients and differentiate them into iPSC-derived cardiomyocytes as well as house the DMD/BMD Biobank, which will store relevant clinical data as well as validated guide RNAs for each genetic mutation, and (C) a Training Core, which will enhance the educational environment in order to recruit, train, and maintain the next generation of transformative investigators focused on addressing the challenges of muscular dystrophy. We firmly believe myoediting will offer an innovative therapeutic modality for the treatment of many thousands of DMD patients and offer a long awaited hope to these patients and their families devastated by DMD.