RNAi therapy for dominant muscular dystrophies and other myopathies

Abstract

Over the last ∼15 years, muscular dystrophy gene therapy strategies have been primarily aimed at replacing defective or missing genes underlying recessive disorders, such as Duchenne muscular dystrophy. These gene replacement strategies are typically not indicated for treating dominant diseases; instead, patients bearing dominant mutations would likely benefit from reduction or elimination of the abnormal allele. Until very recently, there was no feasible mechanism to reduce or eliminate disease genes, and molecular therapy development for dominant muscular dystrophies was largely unexplored. RNA interference (RNAi) has recently emerged as a powerful tool to suppress any gene of interest in a sequence-specific manner. As such, RNAi is a leading candidate strategy to silence dominant disease genes, including those involved in muscular dystrophy and related myopathies. Here, we discuss the potential for RNAi-mediated gene therapy of dominant muscular dystrophies and other myopathies.