Duchenne muscular dystrophy (DMD) is an inherited X-linked disease caused by mutations in the gene encoding dystrophin, a protein required for muscle fiber integrity. Dystrophin is a large cytoskeletal structural protein essential formuscle cellmembrane integrity. Without it, muscles degenerate, causing weakness and myopathy.
DMD affects approximately 1 in 3500 boys, death of patients usually occurs by age 25, typically from breathing complications and cardiomyopathy. Hence, therapy for DMD necessitates sustained rescue of skeletal, respiratory, and cardiac muscle structure and function. Although the genetic cause of DMD was identified nearly three decades ago, and several gene- and cell-based therapies have been developed to deliver functional Dmd alleles or dystrophin-like protein to diseased muscle tissue, numerous therapeutic challenges have remained and presently and there is no effective treatment.
In a recent study, researchers used clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)–mediated genome editing to correct the dystrophin gene (Dmd) mutation in the germline of mdx mice, amodel for DMD, and then monitored muscle structure and function. Genome editing produced genetically mosaic animals containing 2 to 100% correction of the Dmd gene.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.With the anticipated technological advances that will facilitate genome editing of postnatal somatic cells, this strategymay one day allowcorrection of disease-causing mutations in the muscle tissue of patients with DMD. (Science, Sept 5 2014)