We have been exploring the feasibility of gene therapy for Duchenne mu
scular 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 b
een accompanied by the development of viral vectors for gene transfer
to dystrophic mdx mouse muscle. Analysis of transgenic mdx mice indica
tes that greater than 50% of the fibers in a muscle group must express
dystrophin to prevent development of a significant dystrophy, and tha
t 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 vec
tors that express moderate levels of dystrophin proteins. Strategies f
or the development of viral vectors able to deliver dystrophin genes t
o muscle include the use of muscle specific regulatory sequences coupl
ed with deletion of viral gene sequences to limit virus-induced immune
rejection of transduced tissues. These strategies should enable produ
ction of adenoviral vectors expressing full-length dystrophin proteins
in muscle. (C) 1997 Elsevier Science B.V.