Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin

Christiana DelloRusso, Jeannine M. Scott, Dennis Hartigan-O'Connor, Giovanni Salvatori, Catherine Barjot, Ann S. Robinson, Robert W. Crawford, Susan V. Brooks, Jeffrey S. Chamberlain

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Duchenne muscular dystrophy is a lethal X-linked recessive disorder caused by mutations in the dystrophin gene. Delivery of functionally effective levels of dystrophin to immunocompetent, adult mdx (dystrophin-deficient) mice has been challenging because of the size of the gene, immune responses against viral vectors, and inefficient infection of mature muscle. Here we show that high titer stocks of three different gutted adenoviral vectors carrying full-length, muscle-specific, dystrophin expression cassettes are able to efficiently transduce muscles of 1-yr-old mdx mice. Single i.m. injections of viral vector restored dystrophin production to 25-30% of mouse limb muscle 1 mo after injection. Furthermore, functional tests of virally transduced muscles revealed almost 40% correction of their high susceptibility to contraction-induced injury. Our results show that functional abnormalities of dystrophic muscle can be corrected by delivery of full-length dystrophin to adult, immunocompetent mdx mice, raising the prospects for gene therapy of muscular dystrophies.

Original languageEnglish (US)
Pages (from-to)12979-12984
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number20
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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