Allele-Specific Silencing of Mutant Myh6 Transcripts in Mice Suppresses Hypertrophic Cardiomyopathy

Abstract

Silencing a Silent Killer Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in young athletes. HCM is caused by dominant mutations in genes encoding constituents of the cardiac sarcomere, the contractile unit that keeps the heart pumping. Studying a mouse model that recapitulates a severe form of HCM caused by a mutation in a β myosin heavy chain gene, Jiang et al. (p. 111 ) investigated whether sarcomere dysfunction could be corrected by selectively silencing expression of the mutant allele. Mice treated shortly after birth with a viral vector encoding an appropriately designed RNA interference cassette did not develop cardiac hypertrophy or myocardial fibrosis—the pathologic manifestations of HCM—for at least 6 months.