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Rational design of antisense oligomers to induce dystrophin exon skipping
Journal article   Peer reviewed

Rational design of antisense oligomers to induce dystrophin exon skipping

C. Mitrpant, A.M. Adams, P.L. Meloni, F. Muntoni, S. Fletcher and S.D. Wilton
Molecular Therapy, Vol.17(8), pp.1418-1426
2009
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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.

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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
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