Therapeutic gene editing in muscles and muscle stem cells

Abstract

Duchenne muscular dystrophy (DMD) is a devastating, degenerative muscle disease that affects ~1 in every 3500 male births. DMD arises from mutations in the DMD gene that prevent expression of its encoded protein, Dystrophin (Burghes et al. Nature 328:434–437, 1987). Interestingly, patients with Dmd mutations that delete certain segments of the Dystrophin coding region, but maintain protein reading frame, have a much milder form of the disease, known as Becker Muscular Dystrophy (BMD). This observation has spurred interest in developing “exon skipping” strategies in which certain mutation-containing or mutation-adjacent Dmd exons are intentionally removed in order to restore protein reading frame, and thereby Dystrophin expression, in DMD patients (Beroud et al. Hum Mutat 28:196–202, 2007; Yokota et al. Expert Opin Biol Ther 7:831–842, 2007).