[Gene therapy to muscle diseases: perspective and issues on basic research].
Gene therapy was considered in the treatment of life-threatening muscular dystrophy such as Duchenne muscular dystrophy (DMD). Introduction of 6.3 kb minidystrophin cDNA using adenovirus vector into skeletal muscle of mdx mice was successful, when the recombinant adenovirus was injected during the neonatal period. Recombinant adenovirus, however, evoked strong immunological reactions, when it was injected during the adult stage. The usage of mutant adenovirus, where a full length dystrophin cDNA was inserted instead of all of adenovirus protein genes, might resolve the problems that initial generations of adenovirus vector raised. Upregulation of endogenous utrophin might also give a relief in DMD patients, since introduction of truncated utrophin gene considerably improved phenotypic expression of mdx mice, when introduced as a transgene.
Takeda
S
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Department of Molecular Genetics, National Institute of Neuroscience, National Center of Neurology and Psychiatry.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA; D016189:Dystrophin / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy*; D015854:Up-Regulation; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; D004247:DNA