Project 1

Despite intense efforts to find cures for Duchenne muscular dystrophy (DMD) through a variety of approaches, including myoblast transfer, viral delivery of dystrophin, and oligonucleotide-mediated exon skipping, there remains no cure for this disease. We have recently used clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)-mediated genome editing to correct the dystrophin gene (Dmd) mutation in the germ line of mdx mice, a model for DMD. Genome editing produced mosaic animals containing 2 to 100 percent correction of the Dmd gene. Remarkably, the degree of muscle phenotypic rescue in mosaic mice exceeded the efficiency of gene correction, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle. In contrast to other approaches, which do not correct the underlying cause of DMD, this genome editing approach removes the genetic mutation responsible for the disease, allowing for permanent correction of muscle structure and function. The long-term goal of this project is to optimize and adapt CRISPR/Cas9-mediated genome editing to postnatal muscle and ultimately to leverage this approach to correct DMD mutations in humans. This project represents a close collaboration between clinicians and basic scientists sharing the common goal of advancing an entirely new therapeutic strategy to permanently cure DMD. We refer to this new strategy as “myoediting”.