BRAIN and NERVE－神経研究の進歩59巻10号

2007年10月発行

増大特集 ALS―研究と診療の進歩

RNA干渉によるALSの治療戦略

著者： 横田隆徳¹

所属機関： ¹東京医科歯科大学大学院医歯学総合研究科脳神経機能病態（神経内科）

ページ範囲：P.1187 - P.1194

文献概要

はじめに

　RNA干渉（RNAi）は2本鎖RNAによって配列特異的に遺伝子の発現が抑制される現象で，1998年にFireとMelloらによって報告され，2006年のノーベル医学生理学賞に選ばれた。RNAiはいかなる遺伝子に対してデザインできて，その標的遺伝子の発現抑制効果は他の核酸医薬であるアンチセンス核酸の103～7倍，リボザイムの102～5（自験）高いと言われている。しかもその配列特異性も高く1塩基の違いの認識も可能であり，医療分野におけるその臨床応用については，その発見当初から大きく期待されていた。Small interfering RNA（siRNA）を用いた遺伝子治療の研究は既にウイルス性疾患，悪性腫瘍などで急速に進んでいる。ここでは，ALSへのsiRNAおよびshort hairpin RNA（shRNA）の核酸医薬としての開発の研究現状と問題点について概説する。

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