title: Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscle.
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.
authors.affiliation: Department of Neuromuscular Diseases, Imperial College London, Charing Cross Hospital, W6 8RP London, UK. k.e.wells@imperial.ac.uk
authors.forename: K E
authors.initials: KE
authors.lastname: Wells
authors.forename: S
authors.initials: S
authors.lastname: Fletcher
authors.forename: C J
authors.initials: CJ
authors.lastname: Mann
authors.forename: S D
authors.initials: SD
authors.lastname: Wilton
authors.forename: D J
authors.initials: DJ
authors.lastname: Wells
mesh_terms: D000818:Animals; D001483:Base Sequence; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D015316:Genetic Therapy; D006801:Humans; D006821:Hyaluronoglucosaminidase; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D016189:Dystrophin; D020319:Oligodeoxyribonucleotides, Antisense; D006821:Hyaluronoglucosaminidase