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Identification of receptors for rabies virus-related vectors

Research Project

Project/Area Number 17K19461
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Neuroscience and related fields
Research InstitutionFukushima Medical University

Principal Investigator

Kobayashi Kazuto  福島県立医科大学, 医学部, 教授 (90211903)

Research Collaborator Takeuchi Kosei  
Kato Shigeki  
Fukabori Ryoji  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords逆行性遺伝子導入 / ウィルスベクター / 受容体 / ノックアウトマウス / 結合タンパク質
Outline of Final Research Achievements

Highly efficient retrograde gene transfer vector is a pseudotype of lentiviral vectors with fusion envelope glycoproteins composed of segments from rabies virus and vesicular stomatitis virus glycoproteins. Although this vector system is useful for the functional analysis of the complex brain network, the mechanisms underlying vector entry into nerve terminal regions is unknown. In the present study, we tried to identify the receptors for the vector. The intracranial injection experiment into the brains of some knockout mice for the candidate molecules excluded the possibility that these candidate molecules or metabolites are the receptors. In contrast the injection experiments with some inhibitors for sugar chains suggested the possibility that sialic acids may be involved in the binding of the vector on cell surface.

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで実体の不明であった、RVに関連するベクター系受容体にはシアル酸を持つ糖鎖が関与する可能性が示唆された。本受容体の解明は、神経科学研究に重要な高頻度逆行性遺伝子導入ベクターの神経終末への結合および取り込みの機構を明らかにすることに繋がり、これらのベクターの導入効率を向上させるための有益な情報を提供すると考えられる。また、実際の狂犬病ウィルスの受容体である可能性もあり、本ウィルスの感染を防御あるいは軽減するための臨床応用にも結び付く可能性がある。

Report

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

    (10 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (4 results)

  • [Int'l Joint Research] Navarra University(スペイン)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Enhancement of the transduction efficiency of a lentiviral vector for neuron-specific retrograde gene delivery through the point mutation of fusion glycoprotein type E.2019

    • Author(s)
      Kato S; Sugawara M; Kobayashi K; Kimura K; Inoue K; Takada M; Kobayashi K
    • Journal Title

      J Neurosci Methods

      Volume: 311 Pages: 147-155

    • DOI

      10.1016/j.jneumeth.2018.10.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A note on retrograde gene transfer efficiency and inflammatory response of lentiviral vectors pseudotyped with FuG-E vs. FuG-B2 glycoproteins.2019

    • Author(s)
      Tanabe S; Uezono S; Tsuge H; Fujiwara M; Miwa M; Kato S; Nakamura K; Kobayashi K; Inoue K; Takada M
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3567-3567

    • DOI

      10.1038/s41598-019-39535-1

    • NAID

      120006818701

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene therapy approaches in the non-human primate model of Parkinson’s disease.2017

    • Author(s)
      Pignataro, D., Sucunza, D., Rico, A.J., Dopeso-Reyes, I.G., Roda, E., Rodríguez-Perez, A.I., Labandeira-Garcia, J.L., Broccoli, V., Kato,S., Kobayashi, K., and Lanciego, J.L.
    • Journal Title

      J. Neural Transm.

      Volume: in press Issue: 3 Pages: 575-589

    • DOI

      10.1007/s00702-017-1681-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pseudotyped lentiviral vectors for retrograde gene delivery into target brain regions.2017

    • Author(s)
      Kobayashi K; Inoue K; Tanabe S; Kato S; Takada M; Kobayashi K
    • Journal Title

      Front Neuroanat

      Volume: 11 Pages: 65-65

    • DOI

      10.3389/fnana.2017.00065

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic manipulation of specific neural circuits by use of a viral vector system.2017

    • Author(s)
      Kobayashi, K., Kato, S., and Kobayashi, K.
    • Journal Title

      J. Neural Transm.

      Volume: in press Issue: 1 Pages: 67-75

    • DOI

      10.1007/s00702-016-1674-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 経路選択的な標識・操作技術を応用したマーモセット大脳皮質―基底核 ネットワークの機能マッピング2019

    • Author(s)
      菅原 正晃、加藤成樹、小林和人
    • Organizer
      平成30年度京都大学霊長類研究所共同利用研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Lentiviral vectors pseudotyped with FuG-E and FuG-E2 glycoprotein suitable for retrograde gene transfer into neural networks involveing cerebral cortical areas in nonhuman primates and rodents2018

    • Author(s)
      Yukio Otsuka, Hitomi Tsuge, Shiori Uezono, Soshi Tanabe, Maki Fujiwara, Miki Miwa, Shigeki Kato, Katsuki Nakamura, Kazuto Kobayashi, Ken-ichi Inoue, Masahiko Takada
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2018 Annual Research Report
  • [Presentation] Optimizing the junction of chimeric fusion glycoprotein of a lentiviral vector for higjly neuron-specific retrograde gene transfer2017

    • Author(s)
      Shigeki Kato, Masateru Sugawara, Kazuto Kobayashi
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] The lentiviral vector pseudotyped with FuG-E glycoprotein is more suitable, compared with the FuG-B2 type, for retrograde gene transfer into the cortical input system of primates2017

    • Author(s)
      Hitomi Tsuge, Shiori Uezono, Satoshi Tanabe, Maki Fujiwara, Kiyomi Nagaya, Masateru Sugawara, Miki Miwa, Naho Konoike, Shigeki Kato, Katsuki Nakamura, Kazuto Kobayashi, Kan-ichi Inoue, Masahiko Takada
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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