Selective transduction into parallel fiber or climbing fiber using antibody-displaying viral vector

• Project/Area Number: 24700394
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Gunma University
• Principal Investigator: KONNO Ayumu 群馬大学, 医学(系)研究科(研究院), 助教 (40509048)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ウイルスベクター / 小脳 / 抗体

Outline of Final Research Achievements

The aim of this research is to establish the method for a selective transduction into parallel fiber or climbing fiber in a mouse cerebellum using an antibody-displaying viral vector. To achieve this aim, we made new antibodies against lumenal domain of VGluT1 or VGluT2. We injected the lentiviral vectors displaying these antibodies into mice cerebellum. However, these vectors could not infect specific cells that were expected. To achieve this aim, we need a different approaches such as adeno-associated virus vector.

Research Products

• [Journal Article] One-year follow-up of gene expression by integrase-defective lentiviral vectors and their therapeutic potential in spinocerebellar ataxia model mice. (2014)
  • Author(s): Saida H, Matsuzaki Y, Takayama K, Iizuka A, Konno A, Yanagi S, and Hirai H.
  • Journal Title: Gene Therapy Volume: 21 Issue: 9 Pages: 820-827
  • DOI: 10.1038/gt.2014.60
  • Peer Reviewed
• [Journal Article] Distinct transduction profiles in the CNS via 3 injection routes of AAV9 and the application to generation of a neurodegenerative mouse model. (2014)
  • Author(s): Huda F, Konno A, Matsuzaki Y, Goenawan H, Miyake K, Shimada T, Hirai H
  • Journal Title: Molecular Therapy - Methods and Clinical Development Volume: 1 Pages: 14032-14032
  • DOI: 10.1038/mtm.2014.32
  • Peer Reviewed / Open Access
• [Journal Article] Mutant ataxin-3 with an abnormally expanded polyglutamine chain disrupts dendritic development and metabotropic glutamate receptor signaling in mouse cerebellar purkinje cells (2014)
  • Author(s): Konno A, Shuvaev AN, Miyake N, Miyake K, Iizuka A, Matsuura S, Huda F, Nakamura K, Yanagi S, Shimada T, Hirai H.
  • Journal Title: Cerebellum Volume: 13 Issue: 1 Pages: 29-41
  • DOI: 10.1007/s12311-013-0516-5
  • Peer Reviewed
• [Presentation] Producing animal models of spinocerebellar ataxia type 3 via a viral vector-mediated gene delivery (2015)
  • Author(s): Ayumu Konno, Yasunori Matsuzaki & Hirokazu Hirai
  • Organizer: International Society of Radiation Neurobiology 5th Conference
  • Place of Presentation: Takasaki City Gallery
  • Year and Date: 2015-02-21
• [Presentation] アデノ随伴ウイルスによる小脳全域への遺伝子導入を介した脊髄小脳変性症3型モデル動物の作出 (2014)
  • Author(s): 今野歩、松﨑泰教、平井宏和
  • Organizer: 2014年度包括型脳科学研究推進支援ネットワーク冬のワークショップ
  • Place of Presentation: 東京ガーデンパレス・東京都
  • Year and Date: 2014-12-12
• [Presentation] Production of animal models of spinocerebellar ataxia type 3 by a viral vector-mediated gene delivery (2014)
  • Author(s): Ayumu Konno, Yasunori Matsuzaki, Naoya Ohta, Hirokazu Hirai
  • Organizer: 1st International Symposium of Gunma University Medical Innovation and 6th International Conference on Advanced Micro-Device Engineering
  • Place of Presentation: Kiryu City Performing Arts Center
  • Year and Date: 2014-12-05
• [Presentation] AAV9 vector-mediated production of animal models of spinocerebellar ataxia type 3 (2014)
  • Author(s): Ayumu Konno, Hirokazu Hirai
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜・横浜市
  • Year and Date: 2014-09-13
• [Presentation] Perturbation of mGluR signaling in SCA3 model mice expressing mutant ataxin-3 and the rescue by intravascular administration of AAV9 (2013)
  • Author(s): A. KONNO, A. N. SHUVAEV, S. YANAGI, H. HIRAI
  • Organizer: Neuroscience2013
  • Place of Presentation: San Diego Convention Center, San Diego, California, USA
• [Presentation] Disruption of mGluR signaling in SCA3 model mice expressing mutant ataxin-3 and the partial restoration via intravenous administration of AAV9 (2013)
  • Author(s): A. KONNO, A. N. SHUVAEV, S. YANAGI, H. HIRAI
  • Organizer: 23rd Neuropharmacology Conference
  • Place of Presentation: Sheraton San Diego Hotel and Marina, San Diego, California, USA
• [Presentation] DISRUPTION OF METABOTROPIC GLUTAMATE RECEPTOR SIGNALING AND RESCUE THROUGH INTRAVASCULAR ADMINISTRATION OF AAV9 IN A MOUSE MODEL OF SPINOCEREBELLAR ATAXIA TYPE 3 (2013)
  • Author(s): Ayumu Konno, Anton N. Shuvaev, Noriko Miyake, Koichi Miyake, Shigeru Yanagi, Takashi Shimada, Hirokazu Hirai
  • Organizer: 第19回日本遺伝子治療学会学術集会
  • Place of Presentation: 岡山コンベンションセンター・岡山県岡山市
• [Presentation] Deficient metabotropic glutamate receptor signaling and rescue through intravascular administration of AAV9 in a mouse model of spinocerebellar ataxia type 3 (2013)
  • Author(s): 今野 歩，Anton N Shuvaev，三宅 紀子，三宅 弘一，柳 茂，島田 隆，平井 宏和
  • Organizer: Neuro2013（第36回日本神経科学大会）
  • Place of Presentation: 国立京都国際会館・京都府京都市
• [Presentation] DISRUPTION OF METABOTROPIC GLUTAMATE RECEPTOR SIGNALING AND RESCUE THROUGH INTRAVASCULAR ADMINISTRATION OF AAV9 IN A MOUSE MODEL OF SPINOCEREBELLAR ATAXIA TYPE 3 (2013)
  • Author(s): 今野 歩，Anton N Shuvaev，三宅 紀子，三宅 弘一，柳 茂，島田 隆，平井 宏和
  • Organizer: 第19回遺伝子治療学会
  • Place of Presentation: 岡山コンベンションセンター
• [Presentation] Gene therapy for spinocerebellar ataxia type-3 using trans-blood-brain barrier gene delivery by AAV9
  • Author(s): 今野 歩，Anton N Shuvaev，三宅 紀子，三宅 弘一，柳 茂，島田 隆，平井 宏和
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場・愛知県名古屋市
• [Presentation] Deficient metabotropic glutamate receptor signaling and rescue through intravascular administration of AAV9 in a mouse model of spinocerebellar ataxia type 3
  • Author(s): 今野 歩，Anton N Shuvaev，三宅 紀子，三宅 弘一，柳 茂，島田 隆，平井 宏和
  • Organizer: Neuro2013(第36回日本神経科学大会、第56回日本神経化学会大会、 第23回日本神経回路学会大会)
  • Place of Presentation: 国立京都国際会館