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Drug discovery driven by structural plasticity of RNA

Research Project

Project/Area Number 24241074
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical biology
Research InstitutionThe University of Tokyo

Principal Investigator

Nakamura Yoshikazu  東京大学, 医科学研究所, 名誉教授 (40114590)

Project Period (FY) 2012-10-31 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2015: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2014: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2013: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2012: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Keywordsアプタマー / SELEX / 核酸医薬 / 創薬標的 / アンタゴニスト / アゴニスト / RNA造形力 / 構造生物学 / RNAアプタマー / 疾患標的タンパク質
Outline of Final Research Achievements

Aptamer is a folded single-stranded nucleic acid that binds given molecules. The concept is based on the ability of short (20-80 mer) sequences to fold, in the presence of a target, into unique three-dimensional structures, which allow the aptamer to bind target molecules with high affinity and specificity. In this study, we developed several RNA and/or DNA aptamers by SELEX method to therapeutic target proteins such as Midkine, Autotaxin and FGF2. The therapeutic potency of these aptamers for cancer, fibrosis and bone diseases, respectively, was confirmed in the in vitro (cell-based) and in vivo (animal-based) studies. In collaboration with O. Nureki’s group of The University of Tokyo, we solved the crystal structure of Autotaxin complexed with the aptamer at the 2.0 angstrom resolution, uncovering the inhibitory mechanism and the structure-function relationship.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (46 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Book (2 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Structural basis for specific inhibition of Autotaxin by a DNA aptamer2016

    • Author(s)
      Kato, K., Ikeda, H., Miyakawa, S., Futakawa, S., Nonaka, Y., Fujiwara, M., Aoki, J., Morita, J., Ishitani, R., Nishimasu, H., Nakamura, Y., Nureki, O.
    • Journal Title

      Nature Str. Mol. Biol.

      Volume: 印刷中 Issue: 5 Pages: 1-9

    • DOI

      10.1038/nsmb.3200

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A functional involvement of ABCE1, eukaryotic ribosome recycling factor, in nonstop mRNA decay in Drosophila melanogaster cells2014

    • Author(s)
      (206)Kashima, I., Takahashi, M., Hashimoto, Y., Sakota, E., Nakamura, Y., Inada, T.
    • Journal Title

      Biochimie

      Volume: 106 Pages: 10-16

    • DOI

      10.1016/j.biochi.2014.08.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain2013

    • Author(s)
      Nomura, Y., Tanaka, Y., Fukunaga, J., Fujiwara, K., Chiba, M., Iibuchi, H., Tanaka, T., Nakamura, Y., Kawai, G., Kozu, T., Sakamoto, T.
    • Journal Title

      J Biochem

      Volume: 154 Issue: 6 Pages: 513-519

    • DOI

      10.1093/jb/mvt082

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt22013

    • Author(s)
      Arai, C., Kurahashi, H., Pack, C.-G.., Sako, Y., and Nakamura, Y.
    • Journal Title

      Translation.

      Volume: 1 Issue: 2 Pages: e26574-e26574

    • DOI

      10.4161/trla.26574

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a mouse model with down-regulated U50 snoRNA (SNORD50) expression and its organ-specific phenotypic modulation2013

    • Author(s)
      Soeno, Y., Fujita, K., Kudo, T., Asagiri, M., Kakuta, S., Taya, Y., Shimazu, Y., Sato, K., Kubo, S., Iwakura, Y., Nakamura, Y., Aoba, T.
    • Journal Title

      PLoS ONE

      Volume: 8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element2013

    • Author(s)
      Fukunaga, J., Nomura, Y., Tanaka, Y., Tanaka, T., Nakamura, Y., Kawai, G., Sakamoto, T., Kozu, T.
    • Journal Title

      RNA

      Volume: 19 Issue: 7 Pages: 927-936

    • DOI

      10.1261/rna.037879.112

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The RNA aptamer inhibiting human vesicular endothelial growth factor receptor 1 without affecting the cytokine binding2013

    • Author(s)
      Ohuchi, S., Shibuya, M., Nakamura, Y.
    • Journal Title

      Biochemistry

      Volume: 52 Issue: 13 Pages: 2274-2279

    • DOI

      10.1021/bi301669p

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midkine promotes neuroblastoma through Notch2 signaling2013

    • Author(s)
      Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, Onishi A, Nakamura Y, Kadomatsu K
    • Journal Title

      Cancer Res

      Volume: 73(4) Issue: 4 Pages: 318-327

    • DOI

      10.1158/0008-5472.can-12-3070

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A bipolar functionality of Q/N-rich proteins: Lsm4 amyloid causes clearance of yeast prions2013

    • Author(s)
      Keita Oishi, Hiroshi Kurahashi, Chan-Gi Pack, Yasushi Sako, Yoshikazu Nakamura
    • Journal Title

      Microbiology Open

      Volume: (印刷中) Issue: 3 Pages: 415-430

    • DOI

      10.1002/mbo3.83

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clearance of yeast prions by misfolded multi-transmembrane proteins2013

    • Author(s)
      Chie Arai, Hiroshi Kurahashi, Masao Ishiwata, Keita Oishi, Yoshikazu Nakamura
    • Journal Title

      Biochimie

      Volume: 95 Issue: 6 Pages: 1223-1232

    • DOI

      10.1016/j.biochi.2013.01.009

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evolution of an inhibitory RNA aptamer against T7 RNA polymerase2012

    • Author(s)
      Ohuchi, S., Mori, Y., Nakamura, Y
    • Journal Title

      FEBS Open Bio

      Volume: 2 Issue: 1 Pages: 203-207

    • DOI

      10.1016/j.fob.2012.07.004

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of an efficient Cell-SELEX to generate RNA aptamers against a cell surface protein of interest2015

    • Author(s)
      Takahashi, M., Hashimoto, Y., Sakota, E., Nakamura, Y.
    • Organizer
      The Oligonucleotide Therapeutics Society 11th Annual Meeting
    • Place of Presentation
      Leiden (Netherlands)
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aptamer Therapeutics Targeting Pain and Fibrosis2015

    • Author(s)
      Yoshikazu Nakamura
    • Organizer
      18th A-IMBN Annual Conference & SIMS Opening Ceremony
    • Place of Presentation
      Cheonan Korea
    • Year and Date
      2015-09-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Therapeutic Aptamer Discovery by RiboART System2015

    • Author(s)
      Yoshikazu Nakamura
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      石川県金沢市
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Therapeutic Aptamer Discovery by the RiboART SystemTargeting Lung Fibrosis2015

    • Author(s)
      Yoshikazu Nakamura
    • Organizer
      16th Annual TIDES
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2015-05-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aptamer Therapeutics Targeting Pain and Lung Fibrosis2015

    • Author(s)
      Nakamura, Y.
    • Organizer
      Aptamers 2015
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2015-03-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Aptamer Therapeutics Targeting Lung Fibrosis2014

    • Author(s)
      Nakamura, Y.
    • Organizer
      17th A-IMBN Annual Conference
    • Place of Presentation
      Manila, Philippines
    • Year and Date
      2014-12-01 – 2014-12-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 抗IL-17アプタマーはC57BL/6JマウスにおけるIL-23誘導乾癬様皮膚炎を抑制する2014

    • Author(s)
      長嶺誠和、大瀧菜月、森 重之、佐々木麻子、平本真介、春田和彦、石黒 亮、中村義一
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] AML1 Runt domainとRNAアプタマーの相互作用のNMR解析2014

    • Author(s)
      高田健太、天野亨、永田崇、片平正人、野村祐介、田中陽一郎、中村義一、神津知子、坂本泰一
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNAアプタマーを用いた新規医用材料の開発2014

    • Author(s)
      野村祐介、福井千恵、戸井田瞳、新見伸吾、宮川伸、金玲、中村義一、蓜島由二
    • Organizer
      第36回日本バイオマテリアル学会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-17 – 2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Improvement of the stability of RNA aptamers against Interleukin-17A.2014

    • Author(s)
      Otaki, N., Sasaki, A., Hiramoto, S., Nagamine, M., Mori, S., Kayo, T., Hota, K., Takahashi, M., Haruta, K., Nakamura, Y.
    • Organizer
      American College of Rheumatoloty
    • Place of Presentation
      Boston, USA
    • Year and Date
      2014-11-14 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Characterization of RNA aptamer targeting the DNA binding domain of AML1 protein2014

    • Author(s)
      Takada, K., Amano, R., Tanaka, Y., Nagata, T., Katahira, M., Nakamura, Y., Kozu, T., Sakamoto, T.
    • Organizer
      第41回 国際核酸化学シンポジウム
    • Place of Presentation
      北九州市
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] A eRF3-targeted novel regulatory system in gene expression and apoptosis2014

    • Author(s)
      Hashimoto, Y., Hoshino, S.-I., Nakamura, Y.
    • Organizer
      Joint Australia and Japan RNA Meeting
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2014-11-02 – 2014-11-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Application of atypical RNAi for human diseases2014

    • Author(s)
      Takahashi,M., Nakamura, Y., Hohjoh, H.
    • Organizer
      Joint Australia and Japan RNA (jajRNA) meeting
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2014-11-02 – 2014-11-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Properties of RNA aptamer binding to AML1 Runt domain2014

    • Author(s)
      Amano, R., Nomura, Y., Nagata, T., Kobayashi, N., Mori, Y., Takada, K., Fukunaga, J., Tanaka, Y., Katahira, M., Nakamura, Y., Kozu, T., Sakamoto, T.
    • Organizer
      XXI Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      Poznan, Poland
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ショウジョウバエ細胞においてリボソームリサイクリング因子ABCE1はNonstop mRNA decayに関与する2014

    • Author(s)
      鹿島勳、迫田絵理、中村義一、稲田利文
    • Organizer
      第16回に本RNA学会年会
    • Place of Presentation
      名古屋市
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] A sequence-conserved RNA motif binds to the DNA-recognition site of AML12014

    • Author(s)
      Kozu, T., Fukunaga, J., Nomura, Y., Tanaka, Y., Amano, R., Tanaka, T., Nakamura, Y., Kawai, G., Sakamoto, T.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] NMRによるAML1タンンパク質をRNAアプタマーの相互作用の解析2014

    • Author(s)
      天野亨、野村祐介、永田崇、小林直宏、高田健太、福永淳一、田中陽一郎、片平正人、中村義一、神津知子、坂本泰一
    • Organizer
      日本分光発光学会年次講演会
    • Place of Presentation
      和光市
    • Year and Date
      2014-05-26 – 2014-05-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] The RNA aptamer against midkine suppresses neuroblastoma xenograft growth by attenuating midkine-Notch2 pathway2014

    • Author(s)
      Kishida, S., Mu, P., Miyakawa, S., Fujiwara, M., Abe, T., Sakamoto, K., Nakamura, Y., Kadomatsu, K.
    • Organizer
      Advances in Neuroblastoma Research
    • Place of Presentation
      Cologne, Germany
    • Year and Date
      2014-05-13 – 2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Therapeutic Aptamer Discovery by the RiboART System2014

    • Author(s)
      Y. Nakamura
    • Organizer
      6th Annual AsiaTIDES
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 転写因子AML1に対して複数の結合部位を持つ高親和性RNAアプタマーの解析2013

    • Author(s)
      天野亨、野村祐介、永田崇、小林直宏、森揺子、福永淳一、田中陽一郎、片平正人、中村義一、神津知子、坂本泰一
    • Organizer
      第36回分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mluti-site binding of high affinity aptamer against AML1 Runt domain2013

    • Author(s)
      Ryo Amano, Yusuke Nomura, Takashi Nagata,Naohiro Kobayashi Yoko Mori,Jun-ichi Fukunaga, Yoichiro Tanaka, Masato Katahira, Yoshikazu Nakamura, Tomoko Kozu and Taiichi Sakamoto
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川
    • Related Report
      2013 Annual Research Report
  • [Presentation] Novel Therapeutics for Pain Control with RNA Aptamer against Nerve Growth Factor2013

    • Author(s)
      Yoshikazu Nakamura
    • Organizer
      Aptamers in Medicine and Perspectives
    • Place of Presentation
      Naples (Italy)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アプタマー創薬2013

    • Author(s)
      中村義一
    • Organizer
      第15回日本RNA学会年会
    • Place of Presentation
      松山
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 転写因子AML1を標的としたRNAアプタマーによるDNAの擬態2013

    • Author(s)
      天野亨、野村祐介、永田崇、森揺子、福永淳一、田中陽一郎、片平正人、中村義一、神津知子、坂本泰一
    • Organizer
      日本ケミカルバイオロジー学会第8回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Novel Therapeutics for Pain Control with RNA Aptamer against Nerve Growth Factor2013

    • Author(s)
      Nakamura, Y.
    • Organizer
      1st Gene and Immunotherapy Conference
    • Place of Presentation
      Ho Chi Minh City, Vietnam
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 転写因子AML1タンパク質とRNAアプタマーの相互作用解析

    • Author(s)
      天野亨、野村祐介、永田崇、森揺子、福永淳一、田中陽一郎、片平正人、中村義一、神津知子、坂本泰一
    • Organizer
      平成25年度日本生化学会関東支部例会
    • Place of Presentation
      山梨
    • Related Report
      2013 Annual Research Report
  • [Presentation] RNAの造形力を利用したアプタマー創薬

    • Author(s)
      中村義一
    • Organizer
      第4回新たな創薬パラダイムの創出
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] アプタマーの創製と医薬開発、「核酸医薬の創製と応用展開」(和田猛監修)2016

    • Author(s)
      藤原将寿、中村義一
    • Publisher
      シーエムシー出版
    • Related Report
      2015 Annual Research Report
  • [Book] アプタマーを標的とした研究の進展と安全性評価2016

    • Author(s)
      野中洋介、藤原将寿、中村義一
    • Publisher
      技術情報協会書籍出版
    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京大学医科学研究所 RNA医科学社会連携研究部門

    • URL

      http://www.ims.u-tokyo.ac.jp/rnaikagaku/top.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学医科学研究所「RNA医科学」社会連携研究部門

    • URL

      http://www.ims.u-tokyo.ac.jp/rnaikagaku/top.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京大学医科学研究所

    • URL

      http://www.ims.u-tokyo.ac.jp/imsut/jp/

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] IL-17に対するアプタマー及びその使用2014

    • Inventor(s)
      石黒亮、中村義一、春田和彦、君島智代
    • Industrial Property Rights Holder
      全薬工業株式会社、東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-03-20
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] IL-17に対するアプタマー及びその使用2013

    • Inventor(s)
      中村義一、石黒亮、春田和彦、君島智代
    • Industrial Property Rights Holder
      全薬工業株式会社、東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-060817
    • Filing Date
      2013-03-22
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] ミッドカインに対するアプタマー及びその用途2012

    • Inventor(s)
      宮川伸、藤原将寿、中村義一、門松健治、牟萍
    • Industrial Property Rights Holder
      株式会社リボミック、名古屋大
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-255588
    • Filing Date
      2012-11-21
    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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