Development of next-generation nucleic acid medicines based on the anti-influenza viral regulatory antisense RNA
| Project/Area Number |
15K06926
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
System genome science
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
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| 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)
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| 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)
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| Research Collaborator |
SAKAMOTO Ryou
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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 / RIP-RNAseq / RIP-RT PCR / 抗ヒトAgo2抗体 / 抗ヒトHuR抗体 / ヒトインフルエンザウイルス感染 / natural antisense RNA / microRNA / ceRNA ネットワーク / RNA-seq法 / ヒトAgo2抗体 / RISC / IFN-alpha1 antisense RNA / ceRNA network |
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| 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.
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Report
(3 results)
Research Products
(11 results)
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[Book] Clinician's guide to AHCC: evidence-based nutritional Immunotherapy2016
Author(s)
Tominori Kimura, Mikio Nishizawa, Satoshi Ohno, Noriaki Fujii, Kenji Sato, Thomas Walshe, Philip C. Calder, Chantal Matar, Gerald Sonnenfeld, Sho Hangai, Hiroaki Yanagimoto, Anil D. Kulkarni, Shigeru Abe, Judith A. Smith, Koji Wakame, Taisei Nomura, Tatsuya Hisajima etc.
Publisher
International Congress on Nutrition and Integrative Medicine (ICNIM)
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