Publication Date:
2004-11-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goyenvalle, Aurelie -- Vulin, Adeline -- Fougerousse, Francoise -- Leturcq, France -- Kaplan, Jean-Claude -- Garcia, Luis -- Danos, Olivier -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1796-9. Epub 2004 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genethon & CNRS UMR 8115, 1, rue de l'Internationale, Evry, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528407" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Dependovirus/genetics
;
Dystrophin/*genetics/metabolism
;
*Exons
;
*Genetic Therapy
;
Genetic Vectors
;
Introns
;
Mice
;
Mice, Inbred mdx
;
Muscle Contraction
;
Muscle Fibers, Skeletal/immunology/pathology
;
Muscle, Skeletal/metabolism/pathology/physiology
;
Muscular Dystrophy, Animal/genetics/pathology/physiopathology/*therapy
;
Muscular Dystrophy, Duchenne/genetics/pathology/physiopathology/*therapy
;
*Mutation
;
Oligonucleotides, Antisense/*pharmacology
;
RNA Splicing
;
RNA, Messenger/genetics/metabolism
;
RNA, Small Nuclear/genetics/*metabolism
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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