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Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscle
Author(s) -
Wells K.E.,
Fletcher S.,
Mann C.J.,
Wilton S.D.,
Wells D.J.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00904-9
Subject(s) - dystrophin , duchenne muscular dystrophy , mdx mouse , exon skipping , muscular dystrophy , microbiology and biotechnology , in vivo , biology , oligonucleotide , phenotype , chemistry , exon , biochemistry , genetics , dna , gene , alternative splicing
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.