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Development of anti-miRNA oligonucleotides with stable duplexes to control cardiac diseases.

Research Project

Project/Area Number 25293030
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Komatsu Yasuo  国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 研究グループ長 (30271670)

Co-Investigator(Kenkyū-buntansha) 南川 典昭  徳島大学, 大学院医歯薬学研究部, 教授 (40209820)
平野 悠  国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 主任研究員 (70415735)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
KeywordsmicroRNA / アンチセンス / 核酸医薬 / RNA / クロスリンク / オリゴヌクレオチド / miRNA / siRNA / 核酸
Outline of Final Research Achievements

We had previously developed an interstrand cross-link (CL) that covalently conjugates a pair of apurinuc/apyrimidinic sites (AP sites) on complementary DNA duplex. We first examined whether the AP site-based cross-link could be applied to complementary 2′-O-methyl RNA (MeRNA) duplexes. Next, we prepared several MeRNA-based anti-miRNA oligonucleotides (AMOs) having CL duplex at the end(s) of the antisense strand, and investigated relationship between the miRNA inhibition activity and the AMO structure. Interestingly, the AMO having the CL-duplex at both terminals exhibited the highest activity and the inhibitory activity was largely affected by the positions of the duplex in AMO molecules. These results indicate the potency of the present structural basis for developing AMO as therapeutic applications.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (35 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Bienzyme reactions on cross-linked DNA scaffolds for electrochemical analysis.2017

    • Author(s)
      Hirano, Y., Ikegami, M., Kowata, K. and Komatsu, Y.
    • Journal Title

      Bioelectrochemistry

      Volume: 113 Pages: 15-19

    • DOI

      10.1016/j.bioelechem.2016.08.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fabrication and characterization of nanoporous gold on microelectrode.2016

    • Author(s)
      Ikegami, M., Hirano, Y., Mie, Y. and Komatsu, Y.
    • Journal Title

      J. Electroanalytical Chem.

      Volume: 783 Pages: 188-191

    • DOI

      10.1016/j.jelechem.2016.11.023

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nanoporous structure of gold electrode fabricated by anodization and its efficacy for direct electrochemistry of human cytochrome P450.2016

    • Author(s)
      Mie, Y., Ikegami, M. and Komatsu, Y.
    • Journal Title

      10.1246/cl.160164

      Volume: 45 Issue: 6 Pages: 640-642

    • DOI

      10.1246/cl.160164

    • NAID

      130005155033

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a 3’-amino linker with high conjugation activity and its application to covalently cross-link blunt ends of a duplex2016

    • Author(s)
      Keiko Kowata, Naoshi Kojima, Yasuo Komatsu
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 24 Issue: 9 Pages: 2108-2113

    • DOI

      10.1016/j.bmc.2016.03.039

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オリゴヌクレオチドの合成後の化学修飾2016

    • Author(s)
      小松康雄
    • Journal Title

      核酸医薬の創製と応用展開

      Volume: 1 Pages: 104-112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Faithful PCR amplification of an unnatural base pair analog, ImNN:NaOO, with four hydrogen bonds.2015

    • Author(s)
      Tarashima, N., Komatsu, Y., Furukawa, K. and Minakawa, N.
    • Journal Title

      Chem. Eur. J.

      Volume: 21 Issue: 30 Pages: 10688-10695

    • DOI

      10.1002/chem.201501484

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Environmentally Responsive and Bright Fluorescent Probes Possessing Dansyl-modified Oligonucleotides under Hybridization of DNA and RNA.2015

    • Author(s)
      Suzuki, Y. and Komatsu, Y.
    • Journal Title

      RNA Technologies

      Volume: -

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Analysis of beat fluctuations and oxygen consumption in cardiomyocytes by scanning electrochemical microscopy.2014

    • Author(s)
      Hirano, Y., Kodama, M., Shibuya, M., Maki, Y. and Komatsu, Y.
    • Journal Title

      Anal. Biochem.

      Volume: 447C Pages: 39-42

    • DOI

      10.1016/j.ab.2013.11.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p-Aminothiophenol modification on gold surface improves stability for electrochemically driven cytochrome P450 microsome activity.2014

    • Author(s)
      Mie, Y., Tateyama, E. and Komatsu, Y.
    • Journal Title

      Electrochim. Acta

      Volume: 115 Pages: 364-369

    • DOI

      10.1016/j.electacta.2013.10.170

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a scanning electrochemical microscopy-based micropipette and its application to analysis of topographic change of single-cell2013

    • Author(s)
      平野 悠
    • Journal Title

      bioelectrochemistry

      Volume: 92 Pages: 1-5

    • DOI

      10.1016/j.bioelechem.2013.01.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of dansyl-modified oligonucleotide probes responding to structural changes in a duplex.2013

    • Author(s)
      Suzuki, Y., Kowata, K. and Komatsu, Y.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 23 Issue: 22 Pages: 6123-6126

    • DOI

      10.1016/j.bmcl.2013.09.017

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Electrochemistry of Microsomal Human Flavin-containing Monooxygenases 1 and 3 on Naphthalenethiol Thin Films.2013

    • Author(s)
      Ikegami, M., Mie, Y., Hirano, Y. and Komatsu, Y.
    • Journal Title

      Ecs Electrochemistry Letters

      Volume: 2 Issue: 12 Pages: G5-G7

    • DOI

      10.1149/2.003312eel

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 合成オリゴヌクレオチドに対する機能性分子の部位特異的導入法2013

    • Author(s)
      小松 康雄
    • Journal Title

      Pharm Tech Japan

      Volume: 29 Pages: 85-90

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 3’-5’ 方向塩基伸長を触媒する tRNA 修飾酵素の基質特異性解析2017

    • Author(s)
      中村彰良、汪 道楽、小松康雄
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学川内北キャンパス(仙台市青葉区)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] アノード溶解によるナノポーラスゴールド形成の電極サイズ依存性2017

    • Author(s)
      池上真志樹、平野 悠、三重安弘、小松康雄
    • Organizer
      第64回応用物理学会春季学術講演会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 走査型電気化学顕微鏡を基盤とした心筋細胞解析システムの開発2016

    • Author(s)
      奥村 翔、平野 悠、小松康雄、牧与志幸
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] クロスリンク2本鎖構造を有する anti-miRNA オリゴ核酸の構造と miRNA 阻害活性との相関2016

    • Author(s)
      三重安弘、平野 悠、小綿恵子、中村彰良、安永茉由、中島芳浩、小松康雄
    • Organizer
      日本核酸医薬学会第2回年会
    • Place of Presentation
      東京理科大学葛飾キャンパス(東京都葛飾区)
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 走査型電気化学顕微鏡を用いた心筋細胞の拍動解析2016

    • Author(s)
      奥村 翔、平野 悠、小松康雄、牧与志幸
    • Organizer
      第25回日本バイオイメージング学会
    • Place of Presentation
      名古屋市立大学薬学部 宮田専治記念ホール(名古屋市瑞穂区)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Structure-function relationship of anti-miRNA oligonucleotides modified with interstrand cross-links.2016

    • Author(s)
      三重安弘、小綿恵子、平野 悠、中村彰良、安永茉由、中島芳浩、小松康雄
    • Organizer
      The 21st Annual Meeting of the RNA Society
    • Place of Presentation
      国立京都国際会館(京都市左京区)
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] クロスリンク2本鎖を有する核酸のmiRNA阻害効果と構造の相関性2016

    • Author(s)
      小綿 恵子、三重 安弘、平野 悠、中村 彰良、安永 茉由、中島 芳浩、小松 康雄
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Electrochemically-assisted enzyme reaction: low cost production and sensitive detection of pharmaceuticals.2016

    • Author(s)
      三重 安弘、池上 真志樹、小松 康雄
    • Organizer
      第15回 LS-BT合同研究発表会
    • Place of Presentation
      産業技術総合研究所、つくば市
    • Year and Date
      2016-02-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 核酸の新規安定化技術の開発と、遺伝子分析ならびに医薬品への応用2016

    • Author(s)
      小松康雄
    • Organizer
      新技術説明会
    • Place of Presentation
      JST東京本部別館ホール(東京都千代田区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Interstrand cross-link of 2′-O-Methyl RNA duplexes and its application as miRNA inhibitors.2015

    • Author(s)
      三重 安弘、平野 悠、小綿 恵子、中村 彰良、安永 茉由、中島 芳浩、小松 康雄
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ、京都市
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Electrochemical Analysis of P450s in Microfluidic Channel.2015

    • Author(s)
      三重 安弘、小松 康雄
    • Organizer
      日本生物物理学会
    • Place of Presentation
      金沢大学、金沢市
    • Year and Date
      2015-09-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 2′-O-Methyl RNA 2本鎖の分子内架橋化反応とmiRNA阻害核酸への展開2015

    • Author(s)
      三重 安弘、平野 悠、小綿 恵子、小松 康雄
    • Organizer
      第17 回日本RNA 学会年会
    • Place of Presentation
      ホテルライフォート札幌、札幌市
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 合成核酸からの分析化学へのアプローチ2014

    • Author(s)
      小松 康雄
    • Organizer
      日本分析化学会第63年会
    • Place of Presentation
      広島大学
    • Year and Date
      2014-09-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] P450電気化学触媒の基盤技術2014

    • Author(s)
      三重 安弘、池上 真志樹、小松 康雄
    • Organizer
      北大ー産総研合同シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2014-08-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Environmentally Responsive and Bright Fluorescent Probes Possessing Dansyl-modified Oligonucleotides under Hybridization of DNA and RNA.2014

    • Author(s)
      鈴木 祥夫、小綿 恵子、小松 康雄
    • Organizer
      Biosensors2014
    • Place of Presentation
      オーストラリア
    • Year and Date
      2014-05-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 査型電気化学顕微鏡を利用した心筋細胞の拍動解析技術の開発

    • Author(s)
      平野 悠, 小玉 実生恵, 牧 与志幸, 渋谷真広, 小松 康雄
    • Organizer
      日本分析化学会第62年会
    • Place of Presentation
      近畿大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] Fluorescent “on-off” Swit ching under Hybridization of DNA and RNA with Dansyl-modified Oligonucleotides.

    • Author(s)
      鈴木 祥夫, 小綿 恵子, 小松 康雄
    • Organizer
      第40回 国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2本鎖間架橋化DNAを活用した電極界面上での酵素反応場の構築

    • Author(s)
      平野 悠, 小玉 実生恵, 小綿 恵子, 池上 真志樹, 小松 康雄
    • Organizer
      薬学会第134年会
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] ゾル-ゲル法で作製される無機多孔質体を用いた核酸合成用担体2016

    • Inventor(s)
      小松康雄、小島直、坂本和也、井上聡、南海浩一
    • Industrial Property Rights Holder
      小松康雄、小島直、坂本和也、井上聡、南海浩一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-002834
    • Filing Date
      2016-01-08
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] マイクロ電極の電極表面の処理方法、表面処理マイクロ電極の製造方法及び表面処理マイクロ電極2015

    • Inventor(s)
      池上真志樹、平野悠、小松康雄
    • Industrial Property Rights Holder
      池上真志樹、平野悠、小松康雄
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-093240
    • Filing Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 核酸架橋体、二本鎖核酸に標的分子を結合させるための化合物、二本鎖核酸に標的分子を結合させるための方法及び化合物2015

    • Inventor(s)
      小松康雄、小島直
    • Industrial Property Rights Holder
      小松康雄、小島直
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-122467
    • Filing Date
      2015-06-17
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 核酸複合体、核酸ハイブリダイゼーションの形成方法、医薬組成物、核酸検出用プローブ及び相補鎖核酸複合体2014

    • Inventor(s)
      小松康雄、平野 悠、三重安弘
    • Industrial Property Rights Holder
      小松康雄、平野 悠、三重安弘
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-251847
    • Filing Date
      2014-12-12
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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