Invited Review. The potential for gene therapy in duchenne muscular dystrophy and other genetic muscle diseases

G Karpati, G Acsadi - Muscle & Nerve: Official Journal of the …, 1993 - Wiley Online Library
G Karpati, G Acsadi
Muscle & Nerve: Official Journal of the American Association of …, 1993Wiley Online Library
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 …
Abstract
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.
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