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Development of a novel technique for widespread gene transduction into neurons throughout the primate brain by the use of viral vectors.

Research Project

Project/Area Number 15K14316
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurophysiology / General neuroscience
Research InstitutionKyoto University

Principal Investigator

Kenichi Inoue  京都大学, 霊長類研究所, 助教 (90455395)

Co-Investigator(Renkei-kenkyūsha) TAKADA MASAHIKO  京都大学, 霊長類研究所, 教授 (00236233)
MATSUMOTO MASAYUKI  筑波大学, 医学医療系, 教授 (50577864)
INOUE SATOSHI  国立感染症研究所, 獣医科学部, 室長 (90213157)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経科学 / 脳・神経 / バイオテクノロジー / ウイルスベクター / 霊長類
Outline of Final Research Achievements

We developed a novel experimental technique that realize widespread gene transduction into neurons throughout the primate brain by the use of viral vectors. Recombinant adeno-associated virus (rAAV) vectors constitute a powerful tool for delivering target genes into the brain. Previous studies reported that AAV9 was able to cross the blood-brain barrier, and that systemic application of a self-complementary AAV9 vector to neonatal mice, rats, and cats yielded efficient gene transduction into neurons. However, gene transduction into neurons of neonatal non-human primates has not yet been performed successfully. In this study, we find that intravascular administration of a capsid-modified AAV9 vector to neonatal macaques resulted in widespread gene transduction into neurons throughout the brain. The present data indicate that this technique is useful in creating genetically manipulated primate models of neuropsychiatric disorders and developing their gene therapeutic approaches.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (37 results)

All 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (28 results) (of which Int'l Joint Research: 11 results,  Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.2017

    • Author(s)
      Saga Y, Nakayama Y, Inoue K, Yamagata T, Hashimoto M, Tremblay L, Takada M, Hoshi E
    • Journal Title

      Eur J Neurosci

      Volume: 印刷中 Issue: 9 Pages: 1186-1199

    • DOI

      10.1111/ejn.13421

    • NAID

      120006305932

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain.2017

    • Author(s)
      Tanabe S, Inoue K, Tsuge H, Uezono S, Nagaya K, Fijiwara M, Kato S, Kobayashi K, Takada M
    • Journal Title

      Neurosci Res

      Volume: 印刷中 Pages: 45-52

    • DOI

      10.1016/j.neures.2017.02.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaque.2016

    • Author(s)
      Kimura K,Inoue K, Kuroiwa Y, Tanaka F, Takada M
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 11 Pages: e0166861-e0166861

    • DOI

      10.1371/journal.pone.0166861

    • NAID

      120005954462

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation.2016

    • Author(s)
      Nagai Y, Kikuchi E, Lerchner W, Inoue Ki, Ji B, Eldridge MA, Kaneko H, Kimura Y, Oh-Nishi A, Hori Y, Kato Y, Hirabayashi T, Fujimoto A, Kumata K, Zhang MR, Aoki I, SuharaT, Higuchi M, Takada M, Richmond BJ, Minamimoto T.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 13605-13605

    • DOI

      10.1038/ncomms13605

    • NAID

      120005898960

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Origins of multisynaptic projections from the basal ganglia to the forelimb region of the ventral premotor cortex in macaque monkeys.2016

    • Author(s)
      Ishida H, Inoue K, Takada M, Hoshi E
    • Journal Title

      Eur J Neurosci

      Volume: 43 Issue: 2 Pages: 258-269

    • DOI

      10.1111/ejn.13127

    • NAID

      120005997650

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuronal and behavioral modulations by pathway-selective optogenetic stimulation of the primate oculomotor system.2015

    • Author(s)
      Inoue K, Takada M, Matsumoto M
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 8378-8378

    • DOI

      10.1038/ncomms9378

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distributions of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.2015

    • Author(s)
      Ito T, Inoue K, Takada M
    • Journal Title

      Neuroscience

      Volume: 310 Pages: 128-151

    • DOI

      10.1016/j.neuroscience.2015.09.041

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ウイルスベクターを利用した霊長類における神経ネットワーク操作2017

    • Author(s)
      井上謙一
    • Organizer
      第6回 生理研-霊長研-脳研 合同シンポジウム
    • Place of Presentation
      新潟大学脳研究所統合脳機能研究センター, 新潟
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Prevention of MPTP-induced parkinsonism by recruitment of calbindin into nigral dopamine neurons.2017

    • Author(s)
      Inoue K, Miyachi S, Nishi K, Okado H, Nagai Y, Minamimoto T, Nambu A, Takada M
    • Organizer
      the 12th International Basal Ganglia Society Meeting, IBAGS 2017.
    • Place of Presentation
      Merida, Mexico
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 狂犬病ウイルスベクターを用いた逆行性越シナプス的ラベル法によるマーモセット帯状皮質への入力様式の解明:大脳基底核からの入力について2017

    • Author(s)
      上園志織、柘植仁美、田辺創思、藤原真紀、長屋七奈、長屋清美、井上謙一、高田昌彦
    • Organizer
      第112回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学、長崎
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of primate neural networks by means of modified viral vectors2016

    • Author(s)
      Inoue K
    • Organizer
      NHP Chemogenetics Workshop
    • Place of Presentation
      National Institute of Health, Bethesda, USA
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal and behavioral modulations by pathway-selective optogenetic stimulation of the primate oculomotor system2016

    • Author(s)
      Inoue K, Takada M, Matsumoto M
    • Organizer
      International Symposium on Adaptive Circuit Shift 2016
    • Place of Presentation
      同志社大学寒梅館、京都
    • Year and Date
      2016-03-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 霊長類における光遺伝学を利用した神経回路の選択的操作2016

    • Author(s)
      井上謙一
    • Organizer
      新潟大学脳研究所-生理研合同シンポジウム
    • Place of Presentation
      自然科学研究機構、岡崎
    • Year and Date
      2016-03-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Primate models for elucidating the circuit pathology of nigrostriatal dopamine system2016

    • Author(s)
      Inoue K
    • Organizer
      第39回日本神経科学大会サテライトシンポジウム:大脳基底核の機能と疾患:基礎と臨床
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Origin of multisynaptic projections from the amygdala to the forelimb region of the ventral premotor cortex in macaque monkeys.2016

    • Author(s)
      Ishida M, Inoue K, Takada M, Hoshi E
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] Investigations of spontaneously naturally emerging parkinsonism-cerebellar syndromein an aged Japanese macaque (Macaca fuscata yakui): a potential analogue of multiplesystem atrophy.2016

    • Author(s)
      K.W. McCairn, Ninomiya T, Nagai Y, Go Y, Inoue K, Kimura K, Matsumoto M, Minamimoto M, Isoda M, Takada M
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] Comparison of efficiency of retrograde gene transfer between lentiviral vectors pseudotyped with FuG-E and FuG-B2 glycoprotein in primate brains: Cortical input system.2016

    • Author(s)
      Tsuge H, Uezono S, Tanabe S, Fujiwara M, Nagaya K, Sugawara M, Miwa M, Konoike N, Kato S, Nakamura K, Kobayashi K, Inoue K, Takada M
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] Comparison of the efficiency of retrograde gene transfer between lentiviral vectors pseudotyped with FuG-E and FuG-B2 glycoprotein in primate brains: Striatal input system.2016

    • Author(s)
      Tanabe S, Uezono S, Tsuge H, Fujiwara M, Nagaya K, Sugawara M, Miwa M, Konoike N, Kato S, Nakamura K, Kobayashi K, Inoue K,
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] Use of an optimized chimeric envelope glycoprotein for enhancement of the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain.2016

    • Author(s)
      Inoue K, Tanabe S, Tsuge H, Ueno T, Nagaya K, Fujiwara M, Sugawara M, Kato S, Kobayashi K, Takada M
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vivo electrophysiological evaluation of chanelrhodopsin-2-expressed dorsal root ganglion neurons in adults rats.2016

    • Author(s)
      Seki K, S Wupuer, Umeda T, Inoue K, Kudo M, Takada M
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] Differential adeno-associated virus mediated gene transfer to dorsal root ganglion neurons with different size in common marmosets.2016

    • Author(s)
      Kudo M, S Wupuer, Inoue K, Takada M, Seki K
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜,横浜
    • Related Report
      2016 Annual Research Report
  • [Presentation] 霊長類におけるウイルスベクターを利用した神経回路の光操作2016

    • Author(s)
      井上謙一
    • Organizer
      ルミノジェネティクス研究会
    • Place of Presentation
      KKRホテル熱海,熱海
    • Related Report
      2016 Annual Research Report
  • [Presentation] Multisynaptic projections from the basal nucleus of the amygdala to the ventral premotor cortex in macaque monkeys.2016

    • Author(s)
      Ishida H, Inoue K, Takada M, Hoshi E
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San Diego、USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain.2016

    • Author(s)
      Fujiwara M, Tanabe S, Tsuge H, Uezono S, Nagaya K, Sugawara M, Kato S, Kobayashi K, Inoue K, Takada M
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San Diego、USA
    • Related Report
      2016 Annual Research Report
  • [Presentation] Studying the structure and function of primate brain by using viral vectors2016

    • Author(s)
      Inoue K
    • Organizer
      The 7th International Neural Microcircuit Conference
    • Place of Presentation
      自然科学研究機構 岡崎コンファレンスセンター, 岡崎
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The lentiviral vector pseudotyped with FuG-E glycoprotien is more suitable, compared with FuG-B2, for retrograde gene transfer in the cortical input system of primate brains.2016

    • Author(s)
      Tsuge H, Uezono S, Tanabe S, Fujiwara M, Sugawara M, Miwa M, Konoike N, Kato S, Nakamura K, Kobayashi K, Inoue K, Takada M
    • Organizer
      第6回マーモセット研究会
    • Place of Presentation
      東京大学, 東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] Differences in efficiency of retrograde gene transfer and cytotoxity between lentiviral vectors pseudotyped with FuG-E and FuG-B2 glycoprotein in primate brains.2016

    • Author(s)
      Sugawara M, *Tanabe S, Uezono S, Tsuge H, Fujiwara M, Miwa M, Konoike N, Kato S, Nakamura K, Inoue K, Takada M, Kobayashi K
    • Organizer
      第6回マーモセット研究会
    • Place of Presentation
      東京大学, 東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of primate neural networks by means of modified viral vectors.2015

    • Author(s)
      Inoue K
    • Organizer
      5th NIPS-CIN Joint Symposium
    • Place of Presentation
      生理学研究所、岡崎
    • Year and Date
      2015-11-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Development in a novel maze-task device for macaques to explore the neural mechanisms underlying motor skill learning.2015

    • Author(s)
      Yasukochi R, Inoue K, Takada M
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      Chicago、USA
    • Year and Date
      2015-10-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spontaneously emerging Parkinsonism-cerebellar syndrome in a subspecies of japanese macaque (macaca fuscata yakui): a potential analogue of multiple system atrophy.2015

    • Author(s)
      K.W.McCairn, Nagai Y, Kimura K, Go Y, Inoue K, Isoda M, Minamimoto T, Matsumoto M, Ninomiya T, Takada M
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      Chicago、USA
    • Year and Date
      2015-10-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optogenetic stimulation of the pathway from the frontal eye field to the superior colliculus evokes neuronal and behavioral modulations in monkeys.2015

    • Author(s)
      Inoue K, Takada M, Matsumoto M
    • Organizer
      Neuroscience 2015
    • Place of Presentation
      Chicago、USA
    • Year and Date
      2015-10-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Recruitment of calbindin into nigral dopaminergic neurons prevents from MPTP-induced parkinsonism.2015

    • Author(s)
      Takada M, Inoue K, Miyachi S
    • Organizer
      2nd World Congress on NeuroTherapeutics
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Origins of multisynaptic projections from the basal ganglia to the ventral premotor cortex in macaque monkeys.2015

    • Author(s)
      Ishida H, Inoue K, Takada M, Hoshi E
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場、神戸
    • Year and Date
      2015-07-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of a novel device for elucidating the neural mechanisms of motor skill learning in macaques.2015

    • Author(s)
      Yasukochi R, Inoue K, Takada M
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場、神戸
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
  • [Presentation] Oculomotor manipulations by pathway-selective optogenetics in nonhuman primates.2015

    • Author(s)
      Inoue K, Fujiwara M, Yasukochi R, Nagaya K, Takada M
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場、神戸
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
  • [Book] Gene Therapy for Neurological Disorders: Methods and Protocols, Methods in Molecular Biology, vol 1382 (Manfredsson FP, ed)2016

    • Author(s)
      Kobayashi K, Kato S, Inoue K, Takada M, Kobayashi K
    • Total Pages
      493
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学霊長類研究所 統合脳システム分野 ホームページ

    • URL

      http://www.pri.kyoto-u.ac.jp/sections/systems_neuroscience/index.html

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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