Improved adenoviral vectors for gene therapy of Duchenne muscular dystrophy.

Journal Article (Journal Article)

We have been exploring the feasibility of gene therapy for Duchenne muscular dystrophy by characterizing parameters important for the design of therapeutic protocols. These studies have used transgenic mice to analyze expression patterns of multiple dystrophin vectors, and have been accompanied by the development of viral vectors for gene transfer to dystrophic mdx mouse muscle. Analysis of transgenic mdx mice indicates that greater than 50% of the fibers in a muscle group must express dystrophin to prevent development of a significant dystrophy, and that low-level expression of truncated dystrophins can function very well. These results suggest that gene therapy of DMD will require methods to transduce the majority of fibers in critical muscle groups with vectors that express moderate levels of dystrophin proteins. Strategies for the development of viral vectors able to deliver dystrophin genes to muscle include the use of muscle specific regulatory sequences coupled with deletion of viral gene sequences to limit virus-induced immune rejection of transduced tissues. These strategies should enable production of adenoviral vectors expressing full-length dystrophin proteins in muscle.

Full Text

Duke Authors

Cited Authors

  • Hauser, MA; Amalfitano, A; Kumar-Singh, R; Hauschka, SD; Chamberlain, JS

Published Date

  • July 1997

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 277 - 283

PubMed ID

  • 9267841

International Standard Serial Number (ISSN)

  • 0960-8966

Digital Object Identifier (DOI)

  • 10.1016/s0960-8966(97)00052-7


  • eng

Conference Location

  • England