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Published Online November 4, 2004
Science DOI: 10.1126/science.1104297

Reports

Submitted on August 20, 2004
Accepted on October 15, 2004

Rescue of Dystrophic Muscle Through U7 snRNA-Mediated Exon Skipping

Aurélie Goyenvalle 1, Adeline Vulin 1, Françoise Fougerousse 1, France Leturcq 2, Jean-Claude Kaplan 2, Luis Garcia 1, Olivier Danos 1*

1 Généthon & CNRS UMR 8115, 1, rue de l'Internationale, Evry, France.
2 Laboratoire de Biochimie et de Génétique Moléculaire, Hôpital Cochin, 123 boulevard de Port-Royal, Paris, France.

* To whom correspondence should be addressed.
Olivier Danos , E-mail: danos{at}genethon.fr

Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy (DMD). 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 mRNA of the mdx mouse, by a single administration of an AAV vector expressing antisense sequences linked to a modified U7 short nuclear (sn) RNA. We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy.


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