title: Long-term benefit of adeno-associated virus/antisense-mediated exon skipping in dystrophic mice.
abstract: Many mutations and deletions in the dystrophin gene, responsible for Duchenne muscular dystrophy (DMD), can be corrected at the posttranscriptional level by skipping specific exons. Here we show that long-term benefit can be obtained in the dystrophic mouse model through the use of adeno-associated viral vectors expressing antisense sequences: persistent exon skipping, dystrophin rescue, and functional benefit were observed 74 weeks after a single systemic administration. The therapeutic benefit was sufficient to preserve the muscle integrity of mice up to old age. These results indicate a possible long-term gene therapy treatment of the DMD pathology.
authors.affiliation: Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, University of Rome La Sapienza, 00185 Rome, Italy.
authors.forename: Michela Alessandra
authors.initials: MA
authors.lastname: Denti
authors.forename: Tania
authors.initials: T
authors.lastname: Incitti
authors.forename: Olga
authors.initials: O
authors.lastname: Sthandier
authors.forename: Carmine
authors.initials: C
authors.lastname: Nicoletti
authors.forename: Fernanda Gabriella
authors.initials: FG
authors.lastname: De Angelis
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rizzuto
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
mesh_terms: D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D016372:RNA, Antisense / Q000235:genetics*
chemical_list: D016189:Dystrophin; D016372:RNA, Antisense