Development of novel form of mimic microRNA for microRNA replacement therapy.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical University
• Principal Investigator: OHNO Shinichiro 東京医科大学, 医学部, 講師 (90513680)
• Co-Investigator(Kenkyū-buntansha): 熊谷 勝義 東京医科大学, 医学部, 助教 (20567911) ; 黒田 雅彦 東京医科大学, 医学部, 主任教授 (80251304) ; 原田 裕一郎 東京医科大学, 医学部, 助手 (80570168)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 核酸医薬 / microRNA / miR-34a / 肺がん

Outline of Final Research Achievements

The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghR caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents. Systemic and local injection of ghR-form miR-34a (ghR-34a) suppressed tumor growth in a mouse model of RAS-induced lung cancer. This novel RNA interference (RNAi) technology may provide a novel, safe, and effective nucleic acid drug platform that will increase the clinical usefulness of nucleic acid therapy.

Free Research Field

分子病理学