Inhibition of microRNA functions by novel nucleic acids, iMIR

2014 Fiscal Year Final Research Report

• Project/Area Number: 25640090
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: EGUCHI Yutaka 大阪大学, 医学(系)研究科(研究院), 准教授 (20243206)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Yoshiki 大阪市立大学, 大学院医学研究科, 准教授 (00397556)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Hiroshi 東京大学, 大学院医学系研究科, 特任助教 (00587793) ; OCHIYA Takahiro 独立行政法人国立がん研究センター, 研究所, 分野長 (60192530) ; KURODA Masahiko 東京医科大学, 医学部, 教授 (80251304)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: iMIR / miRNA / 核酸医薬 / miR-16 / miR-21 / miR-122 / C型肝炎ウイルス / アミノ酸アミダイト

Outline of Final Research Achievements

We developed novel nucleic acid iMIR (Inhibitor of miRNA). We constructed various iMIRs targeting miR-16 and miR-21 by joining 3 miRNA-binding sequences (MBS) containing bulge-type imperfect complementarity with amino acid amidites, and found that Gly-Gly-type iMIR and TPA-type iMIR showed strong activity to inhibit miRNA functions, assessed by luciferase reporter assay. We also found that Gly-Gly-type RNA-iMIR and TPA-type RNA-iMIR targeting miR-122 strongly inhibited replication of hepatitis C virus (HCV), and 10-fold more effective than LNAs in inhibiting HCV replication. iMIR treatment of OR6 cells reduced HCV replication without inducing interferon responses or cellular toxicity, suggesting that iMIRs are promising as novel antiviral agents. These results were published in Molecular Therapy-Nucleic Acids (2015, 4, e219).

Free Research Field

分子生物学、細胞生物学