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Generation of episomal RNA viral vector for stem cell gene therapy

Research Project

Project/Area Number 16K19069
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human genetics
Research InstitutionKyoto University

Principal Investigator

Makino Akiko  京都大学, ウイルス・再生医科学研究所, 助教 (30571145)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsウイルスベクター / 幹細胞 / RNAウイルスベクター / 遺伝子治療 / 幹細胞遺伝子治療 / ボルナウイルスベクター / X-SCID / エピソーマル
Outline of Final Research Achievements

Borna disease virus (BoDV) is an RNA virus persistently infecting stem cells. In this study, we aimed to construct a long-term stable gene transfer system that realizes stem cell therapy using the virus. The BoDV vector expressing IL2RG, which is the causative gene of X-SCID, was prepared and inoculated into hematopoietic stem cells. This vector stably expressed the target gene, however, the transduction efficiency was low. The vector in which the G protein was replaced with CnBV-1 increased the efficiency by 15-fold as compared with BoDV. The improved vector significantly increased the efficiency of transduction into stem cells including iPS cells. BoDV vector with X/P gene of VSBV also increased the transduction efficiency. The improved BoDV vector prepared in this study could be a new platform for stem cell gene therapy.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.2017

    • Author(s)
      Yanai M, Sakai M, Makino A, Tomonaga K.
    • Journal Title

      Virol. J

      Volume: 14 Issue: 1 Pages: 126-126

    • DOI

      10.1186/s12985-017-0793-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of Borna Disease Virus Vector for Differentiation of Human iPSCs into Skeletal Muscle Cells2017

    • Author(s)
      Yumiko Komatsu, Dan Takeuchi, Yusuke Yamamoto, Hidetoshi Sakurai, Tomoyuki Honda, Akiko Makino, Yasuhiro Ikeda, Keizo Tomonaga,
    • Organizer
      20th Annual Meeting of the ASGCT
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A double mutation in polymerase L gene enables adaptation of parrot bornavirus-4 to mammalian cell line2017

    • Author(s)
      Clarise B. Garcia, Yukiko Sassa, Akiko Makino, Keizo Tomonaga
    • Organizer
      36th Annual Meeting of the American Society for Virology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ボルナウイルスの宿主域を決定する分子機構とその進化的特徴2017

    • Author(s)
      小森園亮 佐々悠木子 堀江真行 牧野晶子 朝長啓造
    • Organizer
      環境微生物系学会合同大会2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新興ボルナウイルスのG蛋白質を介した感染性の比較2017

    • Author(s)
      酒井 まどか、小森園 亮、柳井 真瑚、堀江 真行、牧野 晶子、朝長 啓造
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Borna disease virus utilizes host mRNA binding proteins, IGF2BPs, for translational regulation2017

    • Author(s)
      Akiko Makino, Keizo Tomonaga
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of possible influences of nuclear actin in forming the viral factories of Borna disease virus and its crosstalk with Cajal bodies.2017

    • Author(s)
      Yuya Hirai, Akiko Makino, Hideyuki Okamura, Keizo Tomonaga
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of BoDV vector for gene delivery to iPSCs2017

    • Author(s)
      Yumiko Komatsu, Yasuhiro Ikeda, Akiko Makino, Keizo Tomonaga
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Comparison of transduction efficiency of pseudotyped BoDV vectors with different envelope G proteins from the genus Bornavirus2017

    • Author(s)
      Madoka Sakai, Ryo Komorizono, Yumiko Komatsu, Sumio Minamiyama, Makoto Urushitani, Akiko Makino, Keizo Tomonaga
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of variegated squirrel bornavirus2016

    • Author(s)
      Akiko Makino, Ryo Komorizono, Bea Garcia, Keizo Tomonaga
    • Organizer
      第64回日本ウイルス学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Improvement of the production of Borna disease virus vector2016

    • Author(s)
      Akiko Makino, Ryo Komorizono, Madoka Sakai, Keizo Tomonaga
    • Organizer
      24th European Society of Gene and Cell Therapy
    • Place of Presentation
      Florence, Italy
    • Year and Date
      2016-10-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of viral particle production in Borna disease virus-infected cells2016

    • Author(s)
      Akiko Makino, Keizo Tomonaga
    • Organizer
      Within host RNA virus persistence: mechanisms and consequences
    • Place of Presentation
      St Andrews, Scotland
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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