Journal article
Dystrophin isoform induction In Vivo by Antisense-mediated alternative splicing
Molecular Therapy, Vol.18(6), pp.1218-1223
2010
Abstract
Antisense oligomer-induced manipulation of dystrophin pre-mRNA processing can remove exons carrying mutations, or exclude exons flanking frameshifting mutations, and restore dystrophin expression in dystrophinopathy models and in Duchenne muscular dystrophy (DMD) patients. Splice intervention can also be used to manipulate the normal dystrophin pre-mRNA processing and ablate dystrophin expression in wild-type mice, with signs of pathology being induced in selected muscles within 4 weeks of commencing treatment. The disruption of normal dystrophin pre-mRNA processing to alter the reading frame can be very efficient and offers an alternative mechanism to RNA silencing for gene suppression. In addition, it is possible to remove in-frame exon blocks from the DMD gene transcript and induce specific dystrophin isoforms that retain partial functionality, without having to generate transgenic animal models. Specific exon removal to yield in-frame dystrophin transcripts will facilitate mapping of functional protein domains, based upon exon boundaries, and will be particularly relevant where there is either limited, or conflicting information as to the consequences of in-frame dystrophin exon deletions on the clinical severity and progression of the dystrophinopathy.
Details
- Title
- Dystrophin isoform induction In Vivo by Antisense-mediated alternative splicing
- Authors/Creators
- S. Fletcher (Author/Creator) - The University of Western AustraliaA.M. Adams (Author/Creator) - The University of Western AustraliaR.D. Johnsen (Author/Creator) - The University of Western AustraliaK. Greer (Author/Creator) - The University of Western AustraliaH.M. Moulton (Author/Creator) - Oregon State UniversityS.D. Wilton (Author/Creator) - The University of Western Australia
- Publication Details
- Molecular Therapy, Vol.18(6), pp.1218-1223
- Publisher
- Nature Publishing Group
- Identifiers
- 991005542647207891
- Copyright
- 2010 The American Society of Gene & Cell Therapy
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- 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