Development of next-generation nucleic acid medicines based on the anti-influenza viral regulatory antisense RNA

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: System genome science
• Research Institution: Ritsumeikan University
• Principal Investigator: Kimura Tomonori 立命館大学, 薬学部, 教授 (40186325)
• Co-Investigator(Kenkyū-buntansha): 西澤 幹雄 立命館大学, 生命科学部, 教授 (40192687) ; 稲葉 宗夫 関西医科大学, 医学部, 非常勤講師 (70115947)
• Co-Investigator(Renkei-kenkyūsha): YOSHIDA Noriyuki 立命館大学, 薬学部, 助教 (10363996) ; JIANG Shiwen (ODAKA Tokifumi) 関西医科大学, 医学部, 助教 (10548746)
• Research Collaborator: SAKAMOTO Ryou
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 制御性RNA / タンパク質非コード性RNA / アンチセンスRNA / 遺伝子発現制御 / Proof-of-Concept実験

Outline of Final Research Achievements

We reported a natural antisense (AS) RNA as an important modulator of IFN-α1 mRNA levels. We showed that IFN-α1 AS promotes IFN-α1 mRNA stability by transient duplex formation and inhibition of miR-1270-induced mRNA decay. Here, we performed a proof-of-concept experiment to verify the AS-mRNA regulatory axis exerts in vivo control over the expression of innate immunity by the proposed actions of IFN-α1 AS. We established a guinea pig model system for influenza virus infection, which encodes a functional MX1 gene, an important antiviral effector in the type I IFN pathway. This system allowed us to investigate the effects of antisense oligoribonucleotides (asORNs) representing functional domains of guinea pig IFN-α1 AS on gpIFN-α1 mRNA levels and, consequently, on viral proliferation in the respiratory tract of influenza virus A-infected animals. The results indicate that, in light of the proposed actions, the asORNs may modulate the level of IFN-α1 mRNA expression in vivo.

Free Research Field

RNA生物学、分子生物学、ウイルス学