Journal article
Antisense Oligonucleotide-induced exon skipping across the human dystrophin gene transcript
Molecular Therapy, Vol.15(7), pp.1288-1296
2007
Abstract
Protein-truncating mutations in the dystrophin gene lead to the most common childhood form of muscle wasting, Duchenne muscular dystrophy. Becker muscular dystrophy, a condition that typically arises from dystrophin gene lesions that do not disrupt the reading frame, clearly indicates that substantial domains of the dystrophin protein are not essential. Potential therapeutic intervention exists during pre-mRNA splicing, whereby selected exons are excised to either remove nonsense mutations or restore the reading frame around frame-shifting mutations from the mature mRNA. Appropriately designed antisense oligonucleotides (AOs), directed at amenable splicing motifs across the dystrophin gene transcript, block exon recognition and/or spliceosome assembly so that targeted exons are removed from the mature mRNA. We describe a panel of AOs designed to induce skipping of every exon within the human dystrophin gene transcript, with the exception of the first and last exons. Every exon targeted in vitro could be removed from the dystrophin mRNA, although some exons are more efficiently excluded than others. No single motif has emerged as a universal AO annealing site for redirection of dystrophin pre-mRNA processing, although the general trend is that the most efficient compounds are directed at motifs in the first half of the target exon.
Details
- Title
- Antisense Oligonucleotide-induced exon skipping across the human dystrophin gene transcript
- Authors/Creators
- S.D. Wilton (Author/Creator)A.M. Fall (Author/Creator)P.L. Harding (Author/Creator)G. McClorey (Author/Creator)C. Coleman (Author/Creator)S. Fletcher (Author/Creator)
- Publication Details
- Molecular Therapy, Vol.15(7), pp.1288-1296
- Publisher
- Nature Publishing Group
- Identifiers
- 991005541932407891
- Copyright
- 2007 The American Society of Gene Therapy
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- Medicine, Research & Experimental
- ESI research areas
- Clinical Medicine