Journal article
The influence of antisense oligonucleotide length on dystrophin exon skipping
Molecular Therapy, Vol.15(1), pp.157-166
2007
Abstract
Antisense oligonucleotides (AOs) can be used to redirect dystrophin pre-messenger RNA (mRNA) processing, to remove selected exons from the mature dystrophin mRNA, to overcome nonsense mutations, and/or restore the reading frame. Redundancy within the dystrophin protein allows some domains to be removed without seriously compromising function. One of the challenges for splicing blockade is to design AOs that efficiently remove targeted exons across the dystrophin pre-mRNA. AOs are initially designed to anneal to the more obvious motifs implicated in the splicing process, such as acceptor or donor splice sites and in silico predicted exonic splicing enhancers. The AOs are evaluated for their ability to induce targeted exon skipping after transfection into cultured myoblasts. Although no single motif has been implicated in the consistent induction of exon skipping, the length of the AO has emerged as an important parameter in designing compounds that redirect dystrophin pre-mRNA processing. We present data from in vitro studies in murine and human cells showing that appropriately designed AOs of 25–31 nucleotides are generally more effective at inducing exon skipping than shorter counterparts. However, there appears to be an upper limit in optimal length, which may have to be established on a case-by-case basis.
Details
- Title
- The influence of antisense oligonucleotide length on dystrophin exon skipping
- Authors/Creators
- P.L. Harding (Author/Creator)A.M. Fall (Author/Creator)K. Honeyman (Author/Creator)S. Fletcher (Author/Creator)S.D. Wilton (Author/Creator)
- Publication Details
- Molecular Therapy, Vol.15(1), pp.157-166
- Publisher
- Nature Publishing Group
- Identifiers
- 991005543745607891
- 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