Long-term benefit of adeno-associated virus/antisense-mediated exon skipping in dystrophic mice.
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.
Denti
Michela Alessandra
MA
Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, University of Rome La Sapienza, 00185 Rome, Italy.
Incitti
Tania
T
Sthandier
Olga
O
Nicoletti
Carmine
C
De Angelis
Fernanda Gabriella
FG
Rizzuto
Emanuele
E
Auricchio
Alberto
A
Musarò
Antonio
A
Bozzoni
Irene
I
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*
D016189:Dystrophin; D016372:RNA, Antisense