Abstract
The use of antisense oligonucleotides (AOs) to induce exon skipping leading to generation of an in-frame dystrophin protein product could be of benefit in around 70% of Duchenne muscular dystrophy patients. We describe the use of hyaluronidase enhanced electrotransfer to deliver uncomplexed 2'-O-methyl modified phosphorothioate AO to adult dystrophic mouse muscle, resulting in dystrophin expression in 20-30% of fibres in tibialis anterior muscle after a single injection. Although expression was transient, many of the corrected fibres initially showed levels of dystrophin expression well above the 20% of endogenous previously shown to be necessary for phenotypic correction of the dystrophic phenotype.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Dystrophin / chemistry
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Dystrophin / genetics*
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Dystrophin / metabolism
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Electroporation / methods
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Genetic Therapy
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Humans
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Hyaluronoglucosaminidase
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Male
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Mice
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Mice, Inbred mdx
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Muscle, Skeletal / metabolism
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Muscular Dystrophy, Animal / genetics*
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Muscular Dystrophy, Animal / metabolism
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Muscular Dystrophy, Animal / therapy*
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Muscular Dystrophy, Duchenne / genetics
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Muscular Dystrophy, Duchenne / metabolism
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Muscular Dystrophy, Duchenne / therapy
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Oligodeoxyribonucleotides, Antisense / administration & dosage*
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Oligodeoxyribonucleotides, Antisense / chemistry
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Oligodeoxyribonucleotides, Antisense / genetics*
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Transduction, Genetic
Substances
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Dystrophin
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Oligodeoxyribonucleotides, Antisense
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Hyaluronoglucosaminidase