Abstract
For the majority of Duchenne muscular dystrophy (DMD) mutations, antisense oligonucleotide (AON)-mediated exon skipping has the potential to restore a functional protein. Here we show that weekly intravenous injections of morpholino phosphorodiamidate (morpholino) AONs induce expression of functional levels of dystrophin in body-wide skeletal muscles of the dystrophic mdx mouse, with resulting improvement in muscle function. Although the level of dystrophin expression achieved varies considerably between muscles, antisense therapy may provide a realistic hope for the treatment of a majority of individuals with DMD.
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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Drug Administration Schedule
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Dystrophin / genetics*
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Dystrophin / metabolism
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Gene Expression Regulation
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Genetic Therapy
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Humans
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Injections, Intravenous
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred mdx
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Muscle, Skeletal
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Muscular Dystrophy, Animal / genetics
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Muscular Dystrophy, Animal / metabolism
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Muscular Dystrophy, Animal / pathology
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Muscular Dystrophy, Animal / therapy*
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Muscular Dystrophy, Duchenne / genetics
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Muscular Dystrophy, Duchenne / therapy
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Oligodeoxyribonucleotides, Antisense / administration & dosage*
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Oligodeoxyribonucleotides, Antisense / genetics
Substances
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Dystrophin
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Oligodeoxyribonucleotides, Antisense