Publication: Rational design of antisense oligomers to induce dystrophin exon skipping
Issued Date
2009-03-18
Resource Type
ISSN
15250024
15250016
15250016
Other identifier(s)
2-s2.0-68249118707
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Therapy. Vol.17, No.8 (2009), 1418-1426
Suggested Citation
Chalermchai Mitrpant, Abbie M. Adams, Penny L. Meloni, Francesco Muntoni, Sue Fletcher, Steve D. Wilton Rational design of antisense oligomers to induce dystrophin exon skipping. Molecular Therapy. Vol.17, No.8 (2009), 1418-1426. doi:10.1038/mt.2009.49 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/27264
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Rational design of antisense oligomers to induce dystrophin exon skipping
Other Contributor(s)
Abstract
Duchenne muscular dystrophy (DMD), one of the most severe neuromuscular disorders of childhood, is caused by the absence of a functional dystrophin. Antisense oligomer (AO) induced exon skipping is being investigated to restore functional dystrophin expression in models of muscular dystrophy and DMD patients. One of the major challenges will be in the development of clinically relevant oligomers and exon skipping strategies to address many different mutations. Various models, including cell-free extracts, cells transfected with artificial constructs, or mice with a human transgene, have been proposed as tools to facilitate oligomer design. Despite strong sequence homology between the human and mouse dystrophin genes, directing an oligomer to the same motifs in both species does not always induce comparable exon skipping. We report substantially different levels of exon skipping induced in normal and dystrophic human myogenic cell lines and propose that animal models or artificial assay systems useful in initial studies may be of limited relevance in designing the most efficient compounds to induce targeted skipping of human dystrophin exons for therapeutic outcomes.