Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model

Michela Alessandra Denti, Alessandro Rosa, Giuseppe D'Antona, Olga Sthandier, Fernanda Gabriella De Angelis, Carmine Nicoletti, Mariacarmela Allocca, Orietta Pansarasa, Valeria Parente, Antonio Musarò, Alberto Auricchio, Roberto Bottinelli, Irene Bozzoni

Research output: Contribution to journalArticlepeer-review


Duchenne muscular dystrophy is an X-linked muscle disease characterized by mutations in the dystrophin gene. Many of these can be corrected at the posttranscriptional level by skipping the mutated exon. We have obtained persistent exon skipping in mdx mice by tail vein injection with an adeno-associated viral (AAV) vector expressing antisense sequences as part of the stable cellular U1 small nuclear RNA. Systemic delivery of the AAV construct resulted in effective body-wide colonization, significant recovery of the functional properties in vivo, and lower creatine kinase serum levels, suggesting an overall decrease in muscle wasting. The transduced muscles rescued dystrophin expression and displayed a significant recovery of function toward the normal values at single muscle fiber level. This approach provides solid bases for a systemic use of AAV-mediated antisense-U1 small nuclear RNA expression for the therapeutic treatment of Duchenne muscular dystrophy.

Original languageEnglish
Pages (from-to)3758-3763
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
Publication statusPublished - Mar 7 2006


  • Adeno-associated virus vectors
  • Antisense
  • Dystrophin
  • Exon skipping
  • Small nuclear RNA

ASJC Scopus subject areas

  • Genetics
  • General


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