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Gene Ther ; 8(14): 1043-50, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11526451

RESUMO

We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.


Assuntos
Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Fator de Crescimento Insulin-Like I/genética , Músculo Esquelético/fisiologia , Doenças Neuromusculares/terapia , Regeneração , Animais , Células Cultivadas , Expressão Gênica , Membro Posterior , Humanos , Injeções Intramusculares , Fator de Crescimento Insulin-Like I/análise , Óperon Lac , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/análise , Respirovirus/genética , Transfecção/métodos , Transgenes
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