Premium
Invited Review. The potential for gene therapy in duchenne muscular dystrophy and other genetic muscle diseases
Author(s) -
Karpati George,
Acsadi Gyula
Publication year - 1993
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880161102
Subject(s) - dystrophin , duchenne muscular dystrophy , mdx mouse , genetic enhancement , muscular dystrophy , plasmid , skeletal muscle , utrophin , biology , gene , recombinant dna , itga7 , viral vector , microbiology and biotechnology , muscle disorder , myocyte , genetics , medicine , endocrinology
Dystrophin cDNAs have been introduced into skeletal muscle fibers of dystrophin‐deficient mice (mdx) through direct DNA injection in plasmid expression vectors and by replication‐defective recombinant adenovirus vectors. The introduced genes appear to protect those muscle fibers from necrosis in which they become expressed. By direct injection of dystrophin cDNA in plasmid expression vector, only 1–2% of adult mdx muscle fibers of the injected muscle expressed dystrophin. On the other hand, by recombinant adenovirus injection into very young mdx muscle, a better efficiency has been reported. We have discussed several putative and proven factors that may contribute to the thus far demonstrated relatively low efficiency of dystrophin gene transfer. These include poor uptake of gene constructs by muscle fibers, degradation of the injected DNA, and poor access of gene constructs to the nuclear compartment. Neutralization or elimination of these factors could improve the efficiency of gene transfer so that it might, in the future, qualify as an effective therapy for DMD and some other genetic diseases of muscle.© 1993 John Wiley & Sons, Inc.