Development of a novel lentiviral vector system for the research of specific neural circuit labeling through retrograde axonal transport.

• Project/Area Number: 24650169
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Fukushima Medical University
• Principal Investigator: KATO Shigeki 福島県立医科大学, 医学部, 講師 (90443879)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 逆行性レンチウイルスベクター / エンベロープ / 神経回路 / 逆行性遺伝子導入 / レンチウイルスベクター

Research Abstract

We produced various types of fusion glycoproteins, in which the junction between the RVG and VSVG glycoprotein segments diverged in the membrane-proximal region of RVG, and generated HIV-1-based lentiviral vectors pseudotyped with these fusion glycoproteins. We then tested the efficiency of the pseudotyped vectors for the in vivo gene transfer through retrograde transport, comparing that of the NeuRet vector with FuG-C. We found a novel type of fusion glycoprotein, termed type E (FuG-E), that showed improved efficiency of retrograde gene transfer while retaining the property of neuron-specific transduction. This NeuRet vector with FuG-E will provide a powerful tool for genetic treatment of neurological and neurodegenerative diseases and for the study of neural circuit mechanisms underlying various brain functions.

Research Products

• [Journal Article] Improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein (2014)
  • Author(s): Kato, S., Kobayashi, K., and Kobayashi, K.
  • Journal Title: J Neurosci. Methods Volume: 227 Pages: 151-158
  • Peer Reviewed
• [Journal Article] Improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein. (2014)
  • Author(s): Kato, S., Kobayashi, K., and Kobayashi, K.
  • Journal Title: J Neurosci. Methods Volume: 227 Pages: 151-158
  • DOI: 10.1016/j.jneumeth.2014.02.015
  • Peer Reviewed
• [Journal Article] Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice (2013)
  • Author(s): Sooksawate, T., Isa, K., Matsui, R., Kato, S., Kinoshita, M., Kobayashi, K., Watanabe, D., Kobayashi, K., and Isa, T.
  • Journal Title: Front. Neural Circuits Volume: 7 Pages: 162-162
  • Peer Reviewed
• [Journal Article] Highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein (2013)
  • Author(s): Hirano, M., Kato, S., Kobayashi, K., Okada, T., Yaginuma, H., and Kobayashi, K.
  • Journal Title: PLoS ONE Volume: 8(9)
  • Peer Reviewed
• [Journal Article] Elucidating information processing in primate basal ganglia circuitry : a novel technique for pathway-selective ablation mediated by immunotoxin (2013)
  • Author(s): Takada, M., Inoue, K., Koketsu, D., Kato, S., Kobayashi, K., and Nambu, A.
  • Journal Title: Front. Neural Circuits Volume: 7 Pages: 140-140
  • Peer Reviewed
• [Journal Article] Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice. (2013)
  • Author(s): Sooksawate T, Isa K, Matsui R, Kato S, Kinoshita M, Kobayashi K, Watanabe D, Kobayashi K, Isa T.
  • Journal Title: Frontiers in Neural Circuits Volume: 7 Pages: 162-162
  • DOI: 10.3389/fncir.2013.00162
  • Peer Reviewed
• [Journal Article] Highly efficient retrograde gene transfer into motor neurons by lentiviral vector pseudotyped with fusion glycoprotein. (2013)
  • Author(s): Hirano et al.
  • Journal Title: PLos One Volume: 8 Issue: 9 Pages: e75896-e75896
  • DOI: 10.1371/journal.pone.0075896
  • Peer Reviewed
• [Journal Article] Elucidating information processing in primate basal ganglia circuitry: a novel technique for pathway-selective ablation mediated by immunotoxin. (2013)
  • Author(s): Takada et al.
  • Journal Title: Front. Neural Circuits Volume: 7 Pages: 140-140
  • DOI: 10.3389/fncir.2013.00140
  • Peer Reviewed
• [Journal Article] Visualization of the cortical projection neurons by retrograde TET-OFF lentiviral vector. (2012)
  • Author(s): 渡我部昭哉, 他
  • Journal Title: PLos One Volume: 7 Issue: 10 Pages: e46157-e46157
  • DOI: 10.1371/journal.pone.0046157
  • Peer Reviewed
• [Journal Article] Immunotoxin-mediated tract targeting in the primate brain: selective elimination of the cortico-subthalamic "hyperdirect" pathway. (2012)
  • Author(s): Inoue K, Koketsu D, Kato S, Kobayashi K, Nambu A, Takada M
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e39149-e39149
  • DOI: 10.1371/journal.pone.0039149
  • Peer Reviewed
• [Journal Article] Genetic dissection of the circuit for hand dexterity in primates (2012)
  • Author(s): Masaharu Kinoshita, Ryosuke Matsui, Shigeki Kato, Taku Hasegawa, Hironori Kasahara, Kaoru Isa, Akiya Watakabe, Tetsuo Yamamori, Yukio Nishimura, Bror Alstermark, Dai Watanabe, Kazuto Kobayashi & Tadashi Isa
  • Journal Title: Nature Volume: 487 Issue: 7406 Pages: 235-238
  • DOI: 10.1038/nature11206
  • Peer Reviewed
• [Journal Article] ウイルスベクター技術によって脳神経回路の仕組みに迫る (2012)
  • Author(s): 小林 和人, 加藤 成樹, 小林 憲太.
  • Journal Title: 脳21 Volume: 15 Pages: 125-132
• [Presentation] 高頻度逆行性ベクターによる大脳ー小脳ー基底核ネットワークへの遺伝子導入 (2014)
  • Author(s): 加藤成樹, 菅原正晃, 小林和人
  • Organizer: 平成25年度領域ミーティング(CREST)
  • Place of Presentation: 東京・JST東京本部別館1階ホール
  • Year and Date: 2014-03-02
• [Presentation] 刺激弁別学習における2種類の主要な視床線条体路の行動生理学的役割 (2013)
  • Author(s): 加藤成樹, 深堀良二
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2013-12-05
• [Presentation] Functional control of specific neural pathways in basal ganglia circuit by HiRet (2013)
  • Author(s): Shigeki KATO, Ryoji FUKABORI, Kenta Kobayashi, Hiromu Yawo, Yoshikazu Isomura and Kazuto KOBAYASHI
  • Organizer: Neuroscience 2013
  • Place of Presentation: SanDiego, CA, USA・San Diego Convention Center
  • Year and Date: 2013-11-09
• [Presentation] Comparative analysis for behavioral roles of the central lateral and parafascicular nuclear groups projecting to the dorsolateral striatum (2013)
  • Author(s): Shigeki KATO, Ryoji FUKABORI and Kazuto KOBAYASHI
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都・京都国際会館
  • Year and Date: 2013-06-21
• [Presentation] 高頻度逆行性ベクターによる大脳ー小脳ー基底核ネットワークへの遺伝子導入
  • Author(s): 加藤 成樹, 菅原 正晃, 小林 和人
  • Organizer: 平成25年度 領域ミーティング(CREST)
  • Place of Presentation: 東京・JST東京本部別館1階ホール
• [Presentation] 刺激弁別学習における2種類の主要な視床線条体路の行動生理学的役割/Behavioral and physiological roles of two major thalamostriatal pathways in sensory discrimination learning.
  • Author(s): 加藤 成樹, 深堀良二, 小林 和人
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
• [Presentation] Functional control of specific neural pathways in basal ganglia circuit by HiRet.
  • Author(s): Shigeki KATO, Ryoji FUKABORI, Kenta Kobayashi, Hiromu Yawo, Yoshikazu Isomura and Kazuto KOBAYASHI
  • Organizer: Neuroscience 2013
  • Place of Presentation: SanDiego.CA.USA・San Diego Convention Center
• [Presentation] Comparative analysis for behavioral roles of the central lateral and parafascicular nuclear groups projecting to the dorsolateral striatum.
  • Author(s): Shigeki KATO, Ryoji FUKABORI and Kazuto KOBAYASHI
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都・京都国際会館
• [Presentation] 高頻度逆行性ベクターによる大脳ー小脳ー基底核ネットワークへの遺伝子導入
  • Author(s): 加藤成樹、菅原正晃, 伊原寛一郎, 小林和人
  • Organizer: 平成24年度 領域ミーティング(CREST)
  • Place of Presentation: 東京・ベルサール神保町
• [Presentation] 神経回路特異的な機能改変技術を用いた刺激弁別学習における視床線条体神経路の行動生理学的役割の解明
  • Author(s): 加藤成樹、小林和人
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡・福岡国際会議場
• [Presentation] Selective neural pathway targeting reveals key roles of thalamostriatal projection in the control of conditional response association
  • Author(s): Shigeki KATO, Kenta KOBAYASHI, Ryoji FUKABORI, Motokazu UCHIGASHIMA, Masahiko WATANABE, Yuji TSUTSUI and Kazuto KOBAYASHI
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋・名古屋国際会議場
• [Presentation] 学習行動に関わる視床-線条体神経路の機能解析
  • Author(s): 加藤 成樹、小林 和人
  • Organizer: 第27回日本大脳基底核研究会
  • Place of Presentation: 東京・晴海グランドホテル
• [Book] Gene Therapy (Francisco Martin Molina, ed) (2013)
  • Author(s): Kato, S., Kobayashi, K., Inoue, K., Takada, M., and Kobayashi, K. Croatia
  • Publisher: In Tech
• [Book] Gene Therapy (2013)
  • Author(s): Kato, S., Kobayashi, K., Inoue, K., Takada, M., and Kobayashi, K.
  • Total Pages: 12
  • Publisher: InTech