Antisense-mediated modulation of splicing: Therapeutic implications for Duchenne muscular dystrophy

Abstract

While disruption of alternative splicing underlies many diseases, modulation of splicing using antisense oligonucleotides (AONs) can have therapeutic implications. The most notable example is Duchenne muscular dystrophy (DMD), where antisense-mediated exon skipping can restore the open reading frame and allow the synthesis of partly functional dystrophin proteins instead of non-functional ones. This approach is currently tested in early phase clinical trials. In this review the development of the exon skipping approach in patient-derived cell cultures, animal models and patients is described and hurdles that have to be overcome to make this personalized medicine type approach widely applicable are discussed.