title: Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping.
abstract: Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mouse, by a single administration of an AAV vector expressing antisense sequences linked to a modified U7 small nuclear RNA. We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy.
authors.affiliation: Généthon & CNRS UMR 8115, 1, rue de l'Internationale, Evry, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Goyenvalle
authors.forename: Adeline
authors.initials: A
authors.lastname: Vulin
authors.forename: Françoise
authors.initials: F
authors.lastname: Fougerousse
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Kaplan
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D015316:Genetic Therapy; D005822:Genetic Vectors; D007438:Introns; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000276:immunology / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D016189:Dystrophin; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; C405487:U7 small nuclear RNA