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Development of cytokine gene therapy with high therapeutic index by systemic regulation of transgene expression and biological response.

Research Project

Project/Area Number 15H04638
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKyoto University

Principal Investigator

Takakura Yoshinobu  京都大学, 薬学研究科, 教授 (30171432)

Co-Investigator(Kenkyū-buntansha) 高橋 有己  京都大学, 薬学研究科, 准教授 (00547870)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords遺伝子治療 / サイトカイン / プラスミドDNA / ドラッグデリバリー / インターフェロン / 抗原特異的免疫応答
Outline of Final Research Achievements

Interferon-β(IFNβ) is a cytokine with pleiotropic and potent bioactivity. In this study, effective IFNβ gene therapy was developed. First, a plasmid vector named as pMX- IFNβ, which is driven by Mx promoter, was developed to achieve sustained IFNβ transgene expression. Sustained IFNβ expression from pMX- IFNβ was effective in treating cancer and multiple sclerosis (MS) in model mice. Moreover, by designing a fusion protein of galectin-9 (gal9) and IFNβ named as IFNβ-gal9, it was succeeded in improving therapeutic effect of IFNβ on MS and reducing adverse effect of IFNβ. In conclusion, IFN gene therapy with high therapeutic index was successfully developed.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (8 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Safe and effective interferon-beta gene therapy for the treatment of multiple sclerosis by regulating biological activity through the design of interferon-beta-galectin-9 fusion proteins.2018

    • Author(s)
      Hamana A, Takahashi Y, Tanioka A, Nishikawa M, Takakura Y.
    • Journal Title

      Int J Pharm

      Volume: 536 Issue: 1 Pages: 310-317

    • DOI

      10.1016/j.ijpharm.2017.12.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amelioration of Experimental Autoimmune Encephalomyelitis in Mice by Interferon-Beta Gene Therapy, Using a Long-Term Expression Plasmid Vector.2017

    • Author(s)
      Hamana A, Takahashi Y, Tanioka A, Nishikawa M, Takakura Y.
    • Journal Title

      Mol Pharm

      Volume: 14 Issue: 4 Pages: 1212-1217

    • DOI

      10.1021/acs.molpharmaceut.6b01093

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-Inducible Mx Promoter-Driven, Long-Term Transgene Expression System of Interferon-β for Cancer Gene Therapy.2016

    • Author(s)
      Hamana A, Takahashi Y, Nishikawa M, Takakura Y.
    • Journal Title

      Human Gene Therapy

      Volume: 27 Issue: 11 Pages: 936-945

    • DOI

      10.1089/hum.2016.023

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 青色光受容体VIVIDを利用したインターフェロンβの活性制御2017

    • Author(s)
      谷岡あかね、高橋有己、濵名温志、西川元也、高倉喜信
    • Organizer
      第67回日本薬学会近畿支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Sustained expression system of interferon-beta by using interferon-inducible Mx promoter for interferon-beta gene therapy.2016

    • Author(s)
      Atsushi Hamana, Yuki Takahashi, Makiya Nishikawa, Yoshinobu Takakura
    • Organizer
      Globalization of Pharmaceutics Education Network 2016
    • Place of Presentation
      Lawrence, KS, USA
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インターフェロン-β持続発現ベクターの開発とがん遺伝子治療への適用2016

    • Author(s)
      濵名温志、高橋有己、西川元也、高倉喜信
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(横浜県 横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] インターフェロンβ持続発現プラスミドベクターの構築とがん遺伝子治療への適用2015

    • Author(s)
      濵名温志、高橋有己、西川元也、高倉喜信
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都府 京都市)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] インターフェロン応答性Mxプロモーターを利用したインターフェロンβ持続発現プラスミドベクターの開発2015

    • Author(s)
      濵名温志、高橋有己、西川元也、高倉喜信
    • Organizer
      第31回 日本DDS学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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