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A modulator of human innate immunity that affects antiviral type 1 interferon response

Research Project

Project/Area Number 24510283
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field System genome science
Research InstitutionRitsumeikan University

Principal Investigator

KIMURA Tominori  立命館大学, 薬学部, 教授 (40186325)

Co-Investigator(Kenkyū-buntansha) INABA Muneo  関西医科大学, 医学部, 非常勤講師 (70115947)
Co-Investigator(Renkei-kenkyūsha) JIANG Shiwen  立命館大学, 総合科学技術研究機構, 補助研究員 (10548746)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords機能性RNA / long non-coding RNA / natural antisense RNA / nucleic acid medicine / 非コードRNA / 制御性RNA / Natural antisense RNA / Competing endogenous RNA / lncRNA / NAT / ceRNA
Outline of Final Research Achievements

We previously reported natural antisense RNA (AS) as an important modulator of human interferon-α1 (IFN-α1) mRNA levels by promoting the mRNA stability. Present study aims to validate the regulatory role of IFN-α1 AS on the mRNA levels in vivo, thereby, acting as a possible antiviral reagent. We therefore established a guinea pig model system in order to evaluate the effects of IFN-α1 AS in vivo. We employed a biodegradable nanospheres as a drug delivery system, which optimally contained the antisense oligoribonucleotide (ASORN), designed from the stabilization domain sequence of the AS. The nanospheres successfully delivered the ASORN to the human Influenza A virus-infected respiratory tract of the model animals, resulting in the reduction of the viral titers in the respiratory exudates from them. These results thus suggest that the IFN-α1 AS drives the host innate immunity against viral infection in in vivo condition and may lead to therapeutic intervention by the ASORN.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (27 results)

All 2015 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (10 results) (of which Invited: 1 results) Book (2 results) Remarks (10 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Post-transcriptional inducible gene regulation by natural antisense RNA2015

    • Author(s)
      Nishizawa, M., Ikeya, Y., Okumura, T., Kimura, T.
    • Journal Title

      Frontiers in Bioscience (LandMark edition)

      Volume: 20 Issue: 1 Pages: 1-36

    • DOI

      10.2741/4297

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Interferon-alpha competing endogenous RNA network antagonizes microRNA-12702015

    • Author(s)
      Kimura, T., Jiang, S., Yoshida, N., Sakamoto, R., Nishizawa, M.
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 印刷中 Issue: 14 Pages: 2749-2761

    • DOI

      10.1007/s00018-015-1875-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Interleukin-1βinduces tumor necrosis factor-αsecretion from rat hepatocytes2013

    • Author(s)
      Yoshigai E, Hara T, Inaba H, Hashimoto I, Tanaka Y, Kaibori M, Kimura T, Okumura T, Kwon AH, Nishizawa M
    • Journal Title

      Hepatol Res

      Volume: [Epub ahead of print] Issue: 5 Pages: 571-583

    • DOI

      10.1111/hepr.12157

    • Related Report
      2014 Annual Research Report 2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stabilization of human interferon-α1 mRNA by its antisense RNA2013

    • Author(s)
      Tominori Kimura, Shiwen Jiang, Mikio Nishizawa, Emi Yoshigai, Iwao, Hashimoto, Masao Nishikawa, Tadayoshi Okumura, Hisao Yamada
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 70 Issue: 8 Pages: 1451-1467

    • DOI

      10.1007/s00018-012-1216-x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Interferon-alpha1 antisense RNA collaborates with other members of the endogenous interferon-alpha RNA network to antagonize microRNA-12702014

    • Author(s)
      Kimura, T., Yoshida, N., Sakamoto, R., Nishizawa, M.
    • Organizer
      4th Zing Nucelic Acids Conference
    • Place of Presentation
      Cancun, Mexico
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Interferon-alpha1 antisense RNA collaborates with other members of the endogenous interferon-alpha RNA network to antagonize microRNA-12702014

    • Author(s)
      Kimura, T., Yoshida, N., Sakamoto, R., Nishizawa, M.
    • Organizer
      Cell Symposia on Regulatory RNA
    • Place of Presentation
      Berkeley, CA, USA
    • Year and Date
      2014-10-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Stabilisation of human interferon-α1 mRNA by its antisense RNA2012

    • Author(s)
      Tominori Kimura, Shiwen Jiang, Mikio Nishizawa, Emi Yoshigai, Tomoaki Nakano
    • Organizer
      The 22nd CDB Meeting on RNA Sciences in Cell and Developmental Biology II
    • Place of Presentation
      RIKEN Center for Developmental Biolgy,兵庫県
    • Related Report
      2012 Research-status Report
  • [Presentation] Effect of AHCC on IFN-α1 antisense RNA and mRNA expression levels in the respiratory tract of influenza virus A/PR/8/34-infected guinea pigs2012

    • Author(s)
      Shiwen Jiang, Tomoaki Nakano, Mikio Nishizawa, Tominori Kimura
    • Organizer
      The 20th International Congress on Nutrition and Integrative Medicine
    • Place of Presentation
      ホテルロイトン札幌、北海道
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Stabilisation of Human Interferon-α1 mRNA by Its Antisense RNA2012

    • Author(s)
      Tominori Kimura, Shiwen Jiang, Mikio Nisizawa, Emi Yoshigai
    • Organizer
      The Cold Spring Harbor Laboratory 2012 Meeting on Regulatory & Non-coding RNAs
    • Place of Presentation
      New York, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] センダイウイルスにより誘導される内因性アンチセンスRNAによるヒトインターフェロン-α1遺伝子の転写後性発現調節2012

    • Author(s)
      蒋 時文、吉開会美、西澤 幹雄、中村真一朗、木村 富紀
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      グランキューブ大阪、大阪府
    • Related Report
      2012 Research-status Report
  • [Presentation] Effect of AHCC on IFN-α1 antisense RNA and mRNA expression levels: a molecular analysis of action.

    • Author(s)
      Nakano, T., Jiang, S. and Kimura, T.
    • Organizer
      The 21st International Congress on Nutrition and Integrative Medicine (ICNIM 2013)
    • Place of Presentation
      ホテルロイトン札幌 (北海道)
    • Related Report
      2013 Research-status Report
  • [Presentation] 非コード性アンチセンスRNAはcompeting endogenous RNAとしてインターフェロン-α1 mRNAの安定性を制御する.

    • Author(s)
      蒋 時文、中野 智明、木村 富紀
    • Organizer
      第15回日本RNA学会年会
    • Place of Presentation
      愛媛県民文化会館・ひめぎんホール (愛媛県)
    • Related Report
      2013 Research-status Report
  • [Presentation] センダイウイルスにより誘導される内因性アンチセンスRNAによるヒトインターフェロン-α1遺伝子の転写後性発現調節: 分子作用メカニズムの解析

    • Author(s)
      蒋 時文、吉田 徳之、西澤 幹雄、木村 富紀
    • Organizer
      第61回日本ウイルス学会学術集会・総会
    • Place of Presentation
      神戸国際会議場 (兵庫県)
    • Related Report
      2013 Research-status Report
  • [Presentation] A long noncoding antisense RNA regulates the stability of interferon-α1 mRNA by functioning as a competing endogenous RNA.

    • Author(s)
      Jiang, S., Yoshida, N., Nishizawa, M. and Kimura, T.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド (兵庫県)
    • Related Report
      2013 Research-status Report
  • [Book] International Innovation: High Hopes For Health2013

    • Author(s)
      Tominori Kimura
    • Total Pages
      120
    • Publisher
      ResearchMediaLtd
    • Related Report
      2013 Research-status Report
  • [Book] 生命科学1:生物個体から分子へ2012

    • Author(s)
      木村 富紀
    • Total Pages
      215
    • Publisher
      コロナ社
    • Related Report
      2012 Research-status Report
  • [Remarks] Research Story: ウイルス感染治療の創薬につながるアンチセンスRNAの機能を解明する

    • URL

      http://www.ritsumei.ac.jp/research/special/story/story01.html/

    • Related Report
      2014 Annual Research Report
  • [Remarks] FBS: Regulatory long non-coding RNA

    • URL

      https://www.bioscience.org/special-issue-details?editor_id=193

    • Related Report
      2014 Annual Research Report
  • [Remarks] Ritsumeikan Research Story: つながる研究、つなげる研究

    • URL

      http://www.ritsumei.ac.jp/research/special/story/story01.html/

    • Related Report
      2013 Research-status Report
  • [Remarks] Regulatory long non-coding RNA (2014)

    • URL

      http://www.bioscience.org/special-issue-details?editor_id=193

    • Related Report
      2013 Research-status Report
  • [Remarks] F1000Prime Recommended

    • URL

      http://f1000.com/prime/718002947?bd=1&ui=31081

    • Related Report
      2013 Research-status Report
  • [Remarks] User applications: Namalwa cells

    • URL

      http://www.iba-lifesciences.com/Transfection_Applications.html

    • Related Report
      2013 Research-status Report
  • [Remarks] Research Story つながる研究、つなげる研究:Story#1 木村 富紀

    • URL

      http://www.ritsumei.ac.jp/research/special/story/story01.html/

    • Related Report
      2012 Research-status Report
  • [Remarks] FBS/Regulatory long non-coding RNA (2014)

    • URL

      http://www.bioscience.org/special-issue-details?editor_id=193

    • Related Report
      2012 Research-status Report
  • [Remarks] Global Medical Discovery

    • URL

      http://globalmedicaldiscovery.com/key-scientific-articles/stabilization-of-human-interferon-alpha1-mrna-by-its-antisense-rna/

    • Related Report
      2012 Research-status Report
  • [Remarks] F1000Prime/Article Recommendations

    • URL

      http://f1000.com/prime/718002947

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 呼吸器ウイルス感染症の予防・治療剤2015

    • Inventor(s)
      木村 富紀、辻本 広行、塚田 雄亮
    • Industrial Property Rights Holder
      学校法人立命館、ホソカワミクロン株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-005435
    • Filing Date
      2015-01-14
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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