Splicing intervention for Duchenne muscular dystrophy.
The manipulation of pre-mRNA to alter gene transcript splicing patterns offers considerable potential for many genetic disorders. In particular, the targeted removal of one or more exons from a gene transcript can skip over, or compensate for, disease-causing mutations. Duchenne muscular dystrophy (DMD), the most common and severe form of muscular dystrophy, is one such disorder that could benefit from this strategy. Splicing modulation can convert a DMD phenotype into the less severe allelic Becker-like phenotype. Recent studies using antisense oligonucleotide-targeted exon skipping to induce near normal dystrophin in vivo in animal models, and in vitro in DMD cell lines, highlight the promise of this approach. On the basis of these successes, human clinical trials could be realized in the near future.
McClorey
Graham
G
Centre for Neurological and Neuromuscular Disorders, Australian Neuromuscular Research Institute, University of Western Australia, QEII Medical Centre, Nedlands WA 6009, Australia.
Fletcher
Susan
S
Wilton
Stephen
S
D000818:Animals; D016189:Dystrophin / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D012326:RNA Splicing / Q000187:drug effects* / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism
D016189:Dystrophin; D016376:Oligonucleotides, Antisense; D012342:RNA, Small Nuclear