RNA干渉法を用いた筋萎縮性疾患に対する核酸医薬の開発研究

Skeletal muscle is one of the most important morpho-functional organs, and its atrophy causes severe conditions such as muscular dystrophies. RNA interference (RNAi)-based gene therapy has been expected as a safe remedy without side effects. However, the rapid degradation of small interfering RNAs (siRNAs) and their limited duration of activity require efficient delivery methods.
Atelocollagen (ATCOL)- or cationic liposome-mediated administration of siRNAs is a promising approach to disease treatment, including muscular atrophy. In thie study, we used RNAi to control the expression of myostatin, a negative regulator of skeletal muscle formation, for the purpose of developing a good as new method to regulate skeletal muscle volume, and report herein that ATCOL- or cationic liposome-mediated administration of a myostatin-targeting siRNA into skeletal muscles of normal and diseased mice induced a marked increase in muscle mass and a recovery of myofunction. We are now trying to examine the effectiveness of systemic administration of cationic liposome-delivered myostatin-targeting siRNA. Since cationic liposomes delivered siRNA to muscles effectively and are safe and cost-effective, they may represent a powerful therapeutic tool for disease treatment, including muscular atrophy.
In this review, I would like to summarize about possibility to regulate skeletal muscle volume and to develop a new treatment for various muscle disorders by RNAi technique.