In vivo correction of muscular dystrophy

Gene therapy for Duchenne muscular dystrophy has failed to produce long-term stable expression of the dystrophin gene product because of difficulties in gene transfer and adverse immune responses. The recent successful use of chimeric oligonucleotides to repair sickle cell mutations in vivo prompted Bartlett and colleagues to test whether they could efficiently correct a frameshift mutation of the dystrophin gene in the skeletal muscle cells of affected dogs. The researchers designed a chimeric oligonucleotide that would revert a mutation in the splice acceptor site of an intron to the wild-type sequence in vivo, restoring the proper reading frame and production of the full-length gene product. They injected the chimeric oligonucleotide into skeletal muscle of a young affected male dog, and found that sustained repair of the chromosomal mutation could be detected for up to 48 weeks after treatment, along with synthesis of normal-sized dystrophin correctly localized to the sarcoplasmic reticulum. (See pp. 615 and 597).

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Jamison, J. In vivo correction of muscular dystrophy. Nat Biotechnol 18, 586 (2000).

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