Antisense oligonucleotides, exon skipping and the dystrophin gene transcript.

Antisense oligonucleotide induced exon skipping has recently emerged as a potential therapy to by-pass the consequences of many, but not all dystrophin mutations that lead to Duchenne muscular dystrophy. Targeted removal of one or more exons, to restore a disrupted reading frame, or omit a nonsense mutation, could lessen the consequences of an estimated 80% of dystrophin gene mutations. Promising in vitro and in vivo experiments in animal models of dystrophinopathies, as well as demonstration of induced exon skipping in cultured human myogenic cells have prompted considerable enthusiasm. Furthermore, advances in antisense oligonucleotide chemistries have resulted in the development of more stable and less toxic compounds, some of which are currently in Phase III clinical trials for selected antiviral applications. This review will summarize developments in induced exon skipping that have paved the way to clinical trials and some of the challenges and possible limitations.