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Development of gene therapy using self-destructive lentivirus vectors

Research Project

Project/Area Number 16K15319
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionNagasaki University

Principal Investigator

HAYASHI Hideki  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (10218589)

Co-Investigator(Kenkyū-buntansha) 長谷川 寛雄  長崎大学, 病院(医学系), 准教授 (00398166)
Research Collaborator NAKAO Kazuhiko  
KUBO Yoshinao  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsゲノム編集 / 自己削除型レンチウイルスベクター / AAV(アデノ随伴ウイルスベクター)ベクター / CRISPR/Cas9 / 遺伝子治療 / 遺伝子ノックアウト / 「自己削除型」レンチウイルスベクター / 自己削除型ベクター / レンチウイルス / アデノ随伴ウイルスベクター / レンチウイルスベクター / 遺伝子増幅 / 遺伝子 / 癌 / ゲノム / ウィルス / バイオテクノロジー
Outline of Final Research Achievements

We have constructed self-destructive lentivirus vector system for gene therapy against some virus infections integrating their genes into the host genome. However, the lentivirus vector integrated into the genome was not removed by the Tetracycline treatment.
To achieve a practical goal, we first remove the virus gene from the host genome using a lentivirus vector system, and subsequently removed the lentivirus vector from the host genome using AAV (adeno-associated virus) vector system that is not integrated into the host genome generally. The lentivirus was successfully removed from the host genome with some efficacy, though the system was not self-destructive.

Academic Significance and Societal Importance of the Research Achievements

HTLV-1、HBV、HIV等のウイルスは感染すると、宿主細胞ゲノムにウイルス遺伝子を組込み、それぞれATL(成人T細胞白血病)、B型肝炎、AIDSの原因となる。近年、ゲノム上のこれらの遺伝子構造が明らかにされたので、ゲノム編集技術を用いこれらのウイルス遺伝子を除去する治療法を検討した。自己削除型のレンチウイルスシステムを構築したが、試薬誘導による削除ができなかった。そのため、まずレンチウイルスベクターで標的ウイルス遺伝子の除去を行い、次にAAV(アデノ随伴ウイルス)ベクターによりこのゲノム上のレンチウイルスベクターを除去する方法へと変更し、一定の除去が可能となったことは大きな意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017

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

  • [Journal Article] Cytoplasmic R-peptide of murine leukemia virus envelope protein negatively regulates its interaction with the cell surface receptor2019

    • Author(s)
      Kubo Yoshinao、Izumida Mai、Togawa Kei、Zhang Fengmin、Hayashi Hideki
    • Journal Title

      Virology

      Volume: 532 Pages: 82-87

    • DOI

      10.1016/j.virol.2019.04.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of Ezrin Phosphorylation in HIV-1 Replication2018

    • Author(s)
      Kamiyama Haruka、Izumida Mai、Umemura Yuria、Hayashi Hideki、Matsuyama Toshifumi、Kubo Yoshinao
    • Journal Title

      Frontiers in Microbiology

      Volume: 9

    • DOI

      10.3389/fmicb.2018.01912

    • NAID

      120006987949

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines.2018

    • Author(s)
      Hayashi H, Kubo Y, Izumida M, Takahashi E, Kido H, Sato K, Yamaya M, Nishimura H, Nakayama K, Matsuyama T.
    • Journal Title

      Front Cell Infect Microbiol

      Volume: 8 Pages: 91-91

    • DOI

      10.3389/fcimb.2018.00091

    • NAID

      120006937672

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-3662 expression correlates with antiviral drug resistance in adult T-cell leukemia/lymphoma cells.2018

    • Author(s)
      Yasui K, Izumida M, Nakagawa T, Kubo Y, Hayashi H, Ito T, Ikeda H, Matsuyama T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 印刷中 Issue: 4 Pages: 833-837

    • DOI

      10.1016/j.bbrc.2018.04.159

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab3a-Bound CD63 Is Degraded and Rab3a-Free CD63 Is Incorporated into HIV-1 Particles.2017

    • Author(s)
      Kubo Y, Masumoto H, Izumida M, Kakoki K, Hayashi H, Matsuyama T
    • Journal Title

      Front Microbiol

      Volume: 29 Pages: 1653-1653

    • DOI

      10.3389/fmicb.2017.01653

    • NAID

      120006987411

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] カテプシンBはチクングニヤウイルスのエンベロープ蛋白質を介した感染に必須である2018

    • Author(s)
      Mai Izumida,Yoshinao Kubo,Hideki Hayashi,Atsushi Tanaka
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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