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Development of gene delivery system for gene therapy using transsynaptic anterograde viral vectors

Research Project

Project/Area Number 20K21664
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionUniversity of Toyama

Principal Investigator

Ito Tetsufumi  富山大学, 学術研究部医学系, 教授 (90334812)

Co-Investigator(Kenkyū-buntansha) 日置 寛之  順天堂大学, 医学部, 教授 (00402850)
西村 幸司  帝京大学, 医学部, 講師 (20405765)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsウイルスベクター / 経シナプス感染 / 順行性 / 経シナプストレーサー
Outline of Research at the Start

感覚器に障害が起こり活動性が低下すると、それを補償するため神経路全体の興奮性が異常に高まり様々な症状が生じる。耳鳴、慢性疼痛などがその例であり、症状は難治性である。シナプスを超えて輸送される経シナプス順行性ベクターで遺伝子を導入し、経路全体の活動性を下げることができれば、これらの症状を治療できると考えられる。申請者はAvian adeno-associated virus (A3V)が経シナプス順行性ベクターであることを強く示唆する予備的データを得た。本研究はA3Vの性質の確定および改良を試みる。組換えA3Vを感覚器に注入することでその神経路に限局した遺伝子導入・治療が可能になると考える。

Outline of Final Research Achievements

Damage on sensory organs results reduction of neuronal activity, and compensatory plasticity occurs to enhance neuronal activity in the sensory pathway. This is the cause of tinnitus, which is difficult to cure. If we introduce extrinsic gene in the whole sensory pathway, we may reduce the activity in the whole pathway. In this study, we examined the properties of avian adeno-associated virus (A3V) to test whether A3V is suitable to deliver genes in the whole sensory pathway or not. Based on the distribution of labeled cells, the transport direction of A3V is mostly anterograde, and infection spread anterogradely and transsynaptically to several synapses.

Academic Significance and Societal Importance of the Research Achievements

感覚器に障害が起こり活動性が低下すると、低下した活動性を補償するため感覚系神経路全体に可塑的変化が起こり、興奮性が異常に高まって様々な症状が生じる。耳鳴、慢性疼痛、視力障害による幻視などがその例であり、症状は難治性である。もし経路全体に渡って遺伝子導入を行い、経路全体の活動性を下げることができれば、これらの症状を緩和することが可能であろう。本研究で調べたA3Vは外来遺伝子を特定の感覚経路に導入することができ、また毒性も低いため、遺伝子治療ツールとしての潜在性は高い。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (45 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 18 results,  Open Access: 10 results) Presentation (24 results) (of which Invited: 6 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] シカゴ大学(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.2022

    • Author(s)
      Yuta Yoshioka, Yoshihisa Tachibana, Toshihiro Uesaka, Hiroyuki Hioki, Yuya Sato, Takumi Fukumoto, Hideki Enomoto.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 608 Pages: 66-72

    • DOI

      10.1016/j.bbrc.2022.03.117

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multi-scale light microscopy/electron microscopy neuronal imaging from brain to synapse with a tissue clearing method, ScaleSF2022

    • Author(s)
      Furuta Takahiro、Yamauchi Kenta、Okamoto Shinichiro、Takahashi Megumu、Kakuta Soichiro、Ishida Yoko、Takenaka Aya、Yoshida Atsushi、Uchiyama Yasuo、Koike Masato、Isa Kaoru、Isa Tadashi、Hioki Hiroyuki
    • Journal Title

      iScience

      Volume: 25 Issue: 1 Pages: 103601-103601

    • DOI

      10.1016/j.isci.2021.103601

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kv4.2-Positive Domains on Dendrites in the Mouse Medial Geniculate Body Receive Ascending Excitatory and Inhibitory Inputs Preferentially From the Inferior Colliculus2021

    • Author(s)
      Fujimoto Hisataka、Notsu Eiji、Yamamoto Ryo、Ono Munenori、Hioki Hiroyuki、Takahashi Megumu、Ito Tetsufumi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 1-15

    • DOI

      10.3389/fnins.2021.740378

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Avian adeno-associated virus as an anterograde transsynaptic vector2021

    • Author(s)
      Ito Tetsufumi、Ono Munenori、Matsui Ryosuke、Watanabe Dai、Ohmori Harunori
    • Journal Title

      Journal of Neuroscience Methods

      Volume: 359 Pages: 109221-109221

    • DOI

      10.1016/j.jneumeth.2021.109221

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local Connections of Pyramidal Neurons to Parvalbumin-Producing Interneurons in Motor-Associated Cortical Areas of Mice2021

    • Author(s)
      Kuramoto Eriko、Tanaka Yasuhiro R.、Hioki Hiroyuki、Goto Tetsuya、Kaneko Takeshi
    • Journal Title

      eneuro

      Volume: 9 Issue: 1 Pages: 1-20

    • DOI

      10.1523/eneuro.0567-20.2021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Susceptibility of subregions of prefrontal cortex and corpus callosum to damage by high-dose oxytocin-induced labor in male neonatal mice2021

    • Author(s)
      Kitamura Eri、Koike Masato、Hirayama Takashi、Sunabori Takehiko、Kameda Hiroshi、Hioki Hiroyuki、Takeda Satoru、Itakura Atsuo
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 8 Pages: e0256693-e0256693

    • DOI

      10.1371/journal.pone.0256693

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ras-like Gem GTPase induced by Npas4 promotes activity-dependent neuronal tolerance for ischemic stroke2021

    • Author(s)
      Takahashi Hiroo、Asahina Ryo、Fujioka Masayuki、Matsui Takeshi K.、Kato Shigeki、Mori Eiichiro、Hioki Hiroyuki、Yamamoto Tohru、Kobayashi Kazuto、Tsuboi Akio
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 32 Pages: 66-72

    • DOI

      10.1073/pnas.2018850118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proliferating trichilemmal tumor-like neoplasm in the external auditory canal: A case report2021

    • Author(s)
      Fukunaga Y, Kawamoto M, Nishimura K, Hakuba N
    • Journal Title

      Otolaryngology Case Reports.

      Volume: 21 Pages: 100354-100354

    • DOI

      10.1016/j.xocr.2021.100354

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 聴力に異常のないアブミ骨筋腱欠損例2021

    • Author(s)
      北真一郎、山本典生、岡野高之、西村幸司、大森孝一
    • Journal Title

      耳鼻咽喉科臨床

      Volume: 114 Pages: 189-193

    • NAID

      130007993066

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exclusive labeling of direct and indirect pathway neurons in the mouse neostriatum by an adeno-associated virus vector with Cre/lox system2021

    • Author(s)
      Okamoto Shinichiro、Yamauchi Kenta、Sohn Jaerin、Takahashi Megumu、Ishida Yoko、Furuta Takahiro、Koike Masato、Fujiyama Fumino、Hioki Hiroyuki
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 1 Pages: 100230-100230

    • DOI

      10.1016/j.xpro.2020.100230

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tb3+-doped fluorescent glass for biology2021

    • Author(s)
      Okamoto Kazuki、Ebina Teppei、Fujii Naoki、Konishi Kuniaki、Sato Yu、Kashima Tetsuhiko、Nakano Risako、Hioki Hiroyuki、Takeuchi Haruki、Yumoto Junji、Matsuzaki Masanori、Ikegaya Yuji
    • Journal Title

      Science Advances

      Volume: 7 Issue: 2 Pages: 1-8

    • DOI

      10.1126/sciadv.abd2529

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural Basis for Noradrenergic Regulation of Neural Circuits in the Mouse Olfactory Bulb2021

    • Author(s)
      Horie S., Kiyokage E., Hayashi S., Inoue K., Sohn J., Hioki H., Furuta T., Toida K.
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 9 Pages: 2189-2208

    • DOI

      10.1002/cne.25085

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Remodeling of projections from ventral hippocampus to prefrontal cortex in Alzheimer's mice2020

    • Author(s)
      Xu Feng、Ono Munenori、Ito Tetsufumi、Uchiumi Osamu、Wang Furong、Zhang Yu、Sun Peng、Zhang Qing、Yamaki Sachiko、Yamamoto Ryo、Kato Nobuo
    • Journal Title

      Journal of Comparative Neurology

      Volume: 529 Issue: 7 Pages: 1486-1498

    • DOI

      10.1002/cne.25032

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Topographical relationship between the accessory hepatic duct and the hepatic artery system2020

    • Author(s)
      Tanaka Takashi、Nakada Takayuki、Ito Tetsufumi、Kominami Rieko、Sonomura Takahiro、Kagaya Miyuki、Kawai Katsushi、Honma Satoru
    • Journal Title

      Anatomical Science International

      Volume: 96 Issue: 1 Pages: 112-118

    • DOI

      10.1007/s12565-020-00568-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury2020

    • Author(s)
      Tanaka Takashi、Ito Tetsufumi、Sumizono Megumi、Ono Munenori、Kato Nobuo、Honma Satoru、Ueno Masaki
    • Journal Title

      Neurorehabilitation and Neural Repair

      Volume: 34 Issue: 6 Pages: 558-570

    • DOI

      10.1177/1545968320921827

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A hypothalamic novelty signal modulates hippocampal memory2020

    • Author(s)
      Chen Shuo、He Linmeng、Huang Arthur J. Y.、Boehringer Roman、Robert Vincent、Wintzer Marie E.、Polygalov Denis、Weitemier Adam Z.、Tao Yanqiu、Gu Mingxiao、Middleton Steven J.、Namiki Kana、Hama Hiroshi、Therreau Ludivine、Chevaleyre Vivien、Hioki Hiroyuki、Miyawaki Atsushi、Piskorowski Rebecca A.、McHugh Thomas J.
    • Journal Title

      Nature

      Volume: 586 Issue: 7828 Pages: 270-274

    • DOI

      10.1038/s41586-020-2771-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Overlapping Projections of Neighboring Direct and Indirect Pathway Neostriatal Neurons to Globus Pallidus External Segment2020

    • Author(s)
      Okamoto Shinichiro、Sohn Jaerin、Tanaka Takuma、Takahashi Megumu、Ishida Yoko、Yamauchi Kenta、Koike Masato、Fujiyama Fumino、Hioki Hiroyuki
    • Journal Title

      iScience

      Volume: 23 Issue: 9 Pages: 101409-101409

    • DOI

      10.1016/j.isci.2020.101409

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration2020

    • Author(s)
      Katayama Hiroyuki、Hama Hiroshi、Nagasawa Koji、Kurokawa Hiroshi、Sugiyama Mayu、Ando Ryoko、Funata Masaaki、Yoshida Nobuyo、Homma Misaki、Nishimura Takanori、Takahashi Megumu、Ishida Yoko、Hioki Hiroyuki、Tsujihata Yoshiyuki、Miyawaki Atsushi
    • Journal Title

      Cell

      Volume: 181 Issue: 5 Pages: 1176-1187.e16

    • DOI

      10.1016/j.cell.2020.04.025

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 組織透明化技術を介したマクロレベルからナノレベルへのズームイン法2022

    • Author(s)
      日置寛之、山内健太、古田貴寛
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The distribution of GABAergic neuron subtypes in the mouse claustrum.2022

    • Author(s)
      高橋慧、岡本慎一郎、山内健太、小林朋世、小池正人、伊佐正、日置寛之
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] AAV-PHP.eBベクターによる海馬CA2野特異的遺伝子導入2022

    • Author(s)
      岡本和樹、上窪裕二、山内健太、岡本慎一郎、高橋慧、石田葉子、小池正人、池谷裕二、櫻井隆、日置寛之
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Nanobody-based Three-dimensional Immunohistochemical Detection with a Tyramide Signal Amplification Method, FT-GO.2022

    • Author(s)
      山内健太、星野希沙良、石田葉子、小池正人、日置寛之
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Neuronal network structure composed of neocortical inhibitory interneurons2021

    • Author(s)
      日置寛之
    • Organizer
      第10回遺伝研研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Multi-Scale LM/EM Neuronal Imaging from Brain to Synapse with a Tissue Clearing Method2021

    • Author(s)
      日置寛之、山内健太、古田貴寛
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 蛍光チラミド増感法の開発とその応用2021

    • Author(s)
      山内健太、岡本慎一郎、古田貴寛、小池正人、日置寛之
    • Organizer
      日本解剖学会第109回関東支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] AAV2/PHP.eBベクターを用いた海馬CA2野選択的標識2021

    • Author(s)
      岡本和樹、上窪裕二、山内健太、岡本慎一郎、高橋慧、石田葉子、櫻井隆、小池正人、池谷裕二、日置寛之
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 蛍光チラミド増感法の開発とその応用2021

    • Author(s)
      山内健太、岡本慎一郎、古田貴寛、小池正人、日置寛之
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 中枢神経系のネットワーク構造解析2021

    • Author(s)
      日置寛之
    • Organizer
      第8回蛍光イメージング・ミニシンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 耳科学の進歩 蝸牛神経の基礎研究 隠れ難聴の病態解明と再生研究2021

    • Author(s)
      西村幸司
    • Organizer
      第122回日本耳鼻咽喉科学会・学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 両側側頭骨線維性骨異形成症例2021

    • Author(s)
      西村幸司、鈴木大士、長原佳菜、白馬伸洋
    • Organizer
      第31回日本耳科学会総会・学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 3xTgアルツハイマーモデル動物脳内のアミロイドβ蓄積パターンの免疫組織学的解析2021

    • Author(s)
      小野宗範, 伊藤哲史, 堀佳江, 山木幸子, 許峰, 馬蘭蘭, 加藤伸郎
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 内耳損傷の引き起こす下丘におけるニューロンの活動性変化2021

    • Author(s)
      小野宗範, 伊藤 哲史, 馬 蘭蘭, 古山 貴文, 加藤 伸郎
    • Organizer
      日本音響学会聴覚研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 音響外傷により惹起されるマウス下丘興奮性ー抑制性ニューロン活動バランスの改変2021

    • Author(s)
      小野宗範, 伊藤哲史, 馬 蘭蘭, 古山貴文, 加藤伸郎
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新発見の順行性経シナプスウイルスベクターを用いたニワトリ聴覚上行伝導路の解析2021

    • Author(s)
      伊藤 哲史, 小野 宗範, 松井 亮介, 渡邊 大, 大森 治紀
    • Organizer
      日本音響学会聴覚研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 蛍光チラミド増感法の開発とその応用2021

    • Author(s)
      山内健太、岡本慎一郎、古田貴寛、小池正人、日置寛之
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会(合同大会)
    • Related Report
      2020 Research-status Report
  • [Presentation] Multi-Scale LM/EM Neuronal Imaging from Brain to Synapse with a Tissue Clearing Method2021

    • Author(s)
      日置寛之、山内健太、古田貴寛
    • Organizer
      第10回日本マーモセット研究会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 大脳新皮質のグランドデザイン解読を目指して2021

    • Author(s)
      日置寛之
    • Organizer
      第464回医学研究の基礎を語り合う会(東京慈恵会医科大学)
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 大容量電顕データセットを使った視床-大脳皮質神経終末のシナプスターゲット解析2020

    • Author(s)
      窪田芳之、孫在隣、倉本恵梨子、ヨーゼフモハメド、日置寛之、川口泰雄
    • Organizer
      第43回日本神経科学大会(Neuroscience2020)
    • Related Report
      2020 Research-status Report
  • [Presentation] 透明化技術が切り拓くバイオイメージングの新たな展開2020

    • Author(s)
      日置寛之、髙橋慧、山内健太
    • Organizer
      第45回組織細胞化学講習会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 機能的に同定したマウス聴覚野サブ領野への聴覚視床を経由した2シナプス経路の可視化2020

    • Author(s)
      伊藤哲史,劉麗,古山貴文,小野宗範
    • Organizer
      2020年6月度 聴覚研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス後半規管経由ウアバイン局所投与による前庭神経節への影響2020

    • Author(s)
      西村幸司、康本明吉、大森孝一
    • Organizer
      第79回日本めまい平衡医学会総会・学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] Cochlear Implants Meet Regeneration of Primary Auditory Neurons2020

    • Author(s)
      西村幸司
    • Organizer
      第30回日本耳科学会
    • Related Report
      2020 Research-status Report
  • [Book] 決定版 ウイルスベクターによる遺伝子導入実験ガイド2020

    • Author(s)
      平井 宏和、日置 寛之、小林 和人
    • Total Pages
      285
    • Publisher
      羊土社
    • ISBN
      9784758122474
    • Related Report
      2020 Research-status Report
  • [Remarks] 論文の公開

    • URL

      https://syst-funct-morphol.hatenablog.com/entry/2021/05/17/092149?_ga=2.68808981.545306896.1651058778-1674138385.1566471600

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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