標的型ナノ粒子を介してシステム的に投与されたsiRNAからヒトにおけるRNAiの証拠
Mark E Davis1, Jonathan E Zuckerman, Chung Hang J Choi
1Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA. mdavis@cheme.caltech.edu
Nature
|March 23, 2010
まとめ
癌患者の全身的な小干渉RNA (siRNA) 治療は,RNA干渉 (RNAi) の作用メカニズムを示した. この研究は,siRNAがヒトの標的mRNAとタンパク質のレベルを効果的に低下させ,RNAi療法における重要な進歩を示すことを示しています.
科学分野:
- バイオテクノロジー バイオテクノロジー
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- RNA干渉 (RNAi) 治療法は,新しい治療戦略を提供します.
- 小型の干渉RNA (siRNAs) は,インターフェロン反応なしに哺乳類の細胞でRNAiを誘発することができる.
- がん治療のためのsiRNAのシステミックな投与は調査中です.
研究 の 目的:
- 系統的siRNA投与後のヒトにおけるRNAi作用機構の証拠を提供するため.
- がん患者におけるナノ粒子配送のsiRNAの有効性を評価する.
- siRNA治療への反応として標的遺伝子とタンパク質の減少を評価する.
主な方法:
- メラノーマ患者の全身性siRNA投与に関する第I相臨床試験.
- siRNA.RNAのためのターゲティングナノ粒子配送システムを利用しました.
- ナノ粒子の局所化,mRNAおよびタンパク質レベル (RRM2),およびsiRNA媒介の分裂製品のための腫瘍バイオプシを分析しました.
主要な成果:
- 細胞内ナノ粒子は,腫瘍生検で発見され,投与量と相関していました.
- 治療後のRRM2メッセンジャーRNAとタンパク質の濃度の有意な低下が観察されました.
- 高用量患者の予測部位でsiRNA媒介の割れ目を確認するmRNA断片が検出されました.
結論:
- システミックなsiRNA投与は,ヒトにおける特定のRNAi作用機構を誘発することができる.
- ガン患者でRNAiによる遺伝子抑制 (mRNAとタンパク質の減少) が成功していることが実証されています.
- この研究は,システム的に納入されたナノ粒子に関する最初の研究であり,siRNAベースのがん治療のための証拠を提供します.
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