Journal article
Terminal antisense oligonucleotide modifications can enhance induced exon skipping
Neuromuscular Disorders, Vol.15(9-10), pp.622-629
2005
Abstract
Induction of specific exon skipping during the processing of the dystrophin gene transcript is being pursued as a potential therapy for Duchenne muscular dystrophy. Antisense oligonucleotides directed at motifs involved in pre-mRNA processing can manipulate dystrophin exon incorporation in the mature gene transcript. We have compared the exon skipping ability of oligodeoxyribonucleotides with compounds of the identical sequence incorporating 2′-O-methyl modified bases. Antisense oligonucleotides composed entirely of 2′-O-methyl modified bases on a phosphorothioate backbone were consistently more efficient at inducing exon skipping than comparable oligodeoxyribonucleotides. Chimeric antisense oligonucleotides, mixtures of unmodified and 2′-O-methyl modified bases, induced intermediate levels of exon skipping. In addition, we describe terminal modifications that may be incorporated into the 2′-O-methyl antisense oligonucleotides to further enhance efficiency of exon skipping. Our findings suggest that 2′-O-methyl antisense oligonucleotides should be considered for human clinical trials involving targeted exon skipping in dystrophin gene expression in preference to oligodeoxyribonucleotides.
Details
- Title
- Terminal antisense oligonucleotide modifications can enhance induced exon skipping
- Authors/Creators
- B.L. Gebski (Author/Creator)S.J. Errington (Author/Creator)R.D. Johnsen (Author/Creator)S. Fletcher (Author/Creator)S.D. Wilton (Author/Creator)
- Publication Details
- Neuromuscular Disorders, Vol.15(9-10), pp.622-629
- Publisher
- Elsevier BV
- Identifiers
- 991005542035707891
- Copyright
- 2005 Elsevier B.V.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior