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Owing to the development of RNA medicine, discovery of practical RNA molecules and synthesis of nucleic acid PET probes

Research Project

Project/Area Number 24390025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionGifu University

Principal Investigator

KITADE Yukio  岐阜大学, 工学部, 教授 (20137061)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordsRNA創薬 / オリゴヌクレオチド / クリック反応 / ラベル標識化 / 薬物動態 / PETプローブ / バイオイメージング / ドラッグデリバリー / RNA創薬 / ラベル標識 / PETプローブ
Outline of Final Research Achievements

Ethynylbenzene-substituted glycol, as a versatile crick-reaction probe, was synthesized and their RNA post-labeling property was investigated. Stereoselective synthesis of 1-deoxy-1-ethynyl-β-D-ribofuranose was performed for RNA labeling. SiRNAs and miRNAs bearing urea/thioures-bridged aromatic compounds at their 3'-end were also prepared and these dsRNAs definitely showed nuclease resistance. Oligonucleotides with glucosamine at the 3'-position were synthesized reaction and their biological activity was investigated. Some of chemically modified siRNAs at the 3’-position showed avoidance of off-target effect.
Chemically modified synthetic miRNA-205 inhibited the growth of melanoma cells in vitro and in vivo. A clinical trial of miR-205 against canine melanoma is now in progress; thus far, intratumoral injection of miR-205 into a recurrent tumor derived from naturally occurring canine melanoma has resulted in complete remission in 2 of 5 cases.

Report

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

    (30 results)

All 2015 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (19 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Cu/HP20-Catalyzed Solvent-Free Huisgen Cycloaddition at Ordinary Temperatures2014

    • Author(s)
      Yoshiaki Kitamura, Kazumi Taniguchi, Tomohiro Maegawa, Yasunari Monguchi, Yukio Kitade, Hironao Sajiki
    • Journal Title

      HETEROCYCLES

      Volume: 88 Issue: 1 Pages: 233-243

    • DOI

      10.3987/com-13-s(s)6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bioenergetics and Gene Silencing Approaches for Unraveling Nucleotide Recognition by the Human EIF2C2/Ago2 PAZ Domain2014

    • Author(s)
      Mahmoud Kandeel, Abdullah Al-Taher, Remi Nakashima, Tomoya Sakaguchi, Ali Kandeel, Yuki Nagaya, Yoshiaki Kitamura, Yukio Kitade
    • Journal Title

      PLoS One

      Volume: 9 Issue: 5 Pages: e94538-e94538

    • DOI

      10.1371/journal.pone.0094538

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of ethynylbenzene-substituted glycol as a versatile probe for labeling oligonucleotides2014

    • Author(s)
      Qin Ren, Kana Tsunaba, Yoshiaki Kitamura, Remi Nakashima, Aya Shibada, Masato Ikeda, Yukio Kitade.
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 24 Issue: 6 Pages: 1519-1522

    • DOI

      10.1016/j.bmcl.2014.01.082

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemically Modified Synthetic microRNA-205 Inhibits the Growth of Melanoma Cells In Vitro and In Vivo.2013

    • Author(s)
      Noguchi, S., Iwasaki, J., Kumazaki, M., Mori, T., Maruo, K., Saka,i H., Yamada, N., Shimada, K., Naoe, T., Kitade, Y., and Akao, Y.
    • Journal Title

      Mol. Ther.

      Volume: 21 Issue: 6 Pages: 1204-1211

    • DOI

      10.1038/mt.2013.70

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In silico molecular docking analysis of the human Argonaute2 PAZ domain reveals insights into RNA interference2013

    • Author(s)
      M. Kandeel, Y. Kitade
    • Journal Title

      Journal of computer-aided molecular design

      Volume: 27 Issue: 7 Pages: 605-614

    • DOI

      10.1007/s10822-013-9665-3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of oligonucleotides with glucosamine at the 3'-position and evaluation of their biological activity2013

    • Author(s)
      Xiong Luo, Takahiro Sugiura, Remi Nakashima, Yoshiaki Kitamura, Yukio Kitade
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 23 Issue: 14 Pages: 4157-4161

    • DOI

      10.1016/j.bmcl.2013.05.036

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemically modified siRNAs and miRNAs bearing urea/thioures-bridged aromatic compounds at their 3'-end for RNAi therapy2013

    • Author(s)
      Yoshiaki Kitamura, Yuki Masegi, Shunsuke Ogawa, Remi Nakashima, Yukihiro Akao, Yoshihito Ueno, Yukio Kitade
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21 Issue: 15 Pages: 4494-4501

    • DOI

      10.1016/j.bmc.2013.05.046

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Computational Analysis of siRNA Recognition by the Ago2 PAZ Domain and Identification of the Determinants of RNA-Induced Gene Silencing2013

    • Author(s)
      Kandeel Mahmoud, Kitade, Yukio
    • Journal Title

      PLOS ONE

      Volume: 8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective synthesis of 1-deoxy-1-ethynyl-β-D-ribofuranose as a versatile scaffold2012

    • Author(s)
      Yoshiaki Kitamura, Kana Edayoshi, Yukio Kitade
    • Journal Title

      Tetrahedron Letters

      Volume: 53 Issue: 51 Pages: 6987-6989

    • DOI

      10.1016/j.tetlet.2012.10.053

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] グルコサミン結合型 RNA 分子の合成とその機能2015

    • Author(s)
      柴田 綾、溝口 真帆代、喜多村 徳昭、池田 将、北出 幸夫
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 生体親和性グルコサミン結合型RNA分子の合成2014

    • Author(s)
      溝口真帆代、柴田綾、喜多村徳昭、池田将、北出幸夫
    • Organizer
      第45回 中部化学関係学協会支部連合秋季大会
    • Place of Presentation
      中部大学
    • Year and Date
      2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 化学修飾siRNAの合成とそのオフターゲット効果2014

    • Author(s)
      河出美和、中島礼美、喜多村徳昭、北出幸夫
    • Organizer
      日本病院薬剤師会東海ブロック・ 日本薬学会東海支部 合同学術大会2014(第24回日本病院薬剤師会東海ブロック学術大会・ 平成26年度日本薬学会東海支部例会)
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] クリック反応によるPETラベル化RNA合成と評価2014

    • Author(s)
      牧野洋平、仁欽、喜多村徳昭、北出幸夫
    • Organizer
      日本病院薬剤師会東海ブロック・ 日本薬学会東海支部 合同学術大会2014(第24回日本病院薬剤師会東海ブロック学術大会・ 平成26年度日本薬学会東海支部例会)
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthesis of oligonucleotides possessing ethynyl groups and rapid ligand-free click reaction for PET labeling2014

    • Author(s)
      Yoshiaki Kitamura, Qin Ren, Kana Tsunaba, Aya Shibata, Masato Ikeda, Yukio Kitade
    • Organizer
      第41回 国際核酸化学シンポジウム
    • Place of Presentation
      北九州国際会議場
    • Year and Date
      2014-11-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] SYNTHESIS OF OLIGONUCLEOTIDES POSSESSING ETHYNYLBENZENE GLYCOL AND THEIR APPLICATION FOR PET-LABELING2014

    • Author(s)
      Yukio Kitade, Qin Ren, Yoshiaki Kitamura, Remi Nakashima, Aya Shibata and Masato Ikeda
    • Organizer
      21st International Roundtable on Nucleosides, Nucleotides and Nucleic Acids - Chemical Biology of Nucleic Acids
    • Place of Presentation
      PoznanUniversity(ポーランド)
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNA医薬の開発を目指した3’-末端修飾RNAの合成と機能評価2014

    • Author(s)
      喜多村徳昭、小川俊介、Mohmoud Kandeel、北出幸夫
    • Organizer
      第60 回 日本薬学会東海支部総会・大会2014
    • Place of Presentation
      鈴鹿医療科学大学白子キャンパス
    • Year and Date
      2014-07-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] オフターゲット効果の回避を目指した3'末端化学修飾siRNAの合成とその評価2014

    • Author(s)
      河出美和、中島礼美、喜多村徳昭、北出幸夫
    • Organizer
      日本薬学会 第134年会
    • Place of Presentation
      熊本市総合体育館
    • Related Report
      2013 Annual Research Report
  • [Presentation] マラリアTMPキナーゼのヌクレオチド認識能評価2013

    • Author(s)
      マハモウド・カンデイール
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-03-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] オフターゲット効果の回避を目的とした3'末端化学修飾siRNAの開発2013

    • Author(s)
      中島礼美
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-03-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] RNA創薬を目指す塩基部欠損型デオキシリボヌクレオシドの合成2013

    • Author(s)
      長屋優貴、中島礼美、喜多村徳昭、池田将、北出幸夫
    • Organizer
      第59回 日本薬学会東海支部総会・大会
    • Place of Presentation
      名城大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] エチニルベンゼン置換型グリコールを導入した核酸オリゴマーの合成とその性質2013

    • Author(s)
      仁 欽、綱場佳奈、喜多村徳昭、柴田綾、池田将、北出幸夫
    • Organizer
      第59回 日本薬学会東海支部総会・大会
    • Place of Presentation
      名城大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthesis of the chemically modified miRNAs and their anticancer activities2013

    • Author(s)
      Yukio Kitade
    • Organizer
      MicroRNAs Europe 2013 Symposium
    • Place of Presentation
      ケンブリッジ大学(イギリス)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthesis and evaluation of the chemically modified dangling ends on double-stranded RNA: an RNA interference investigation2013

    • Author(s)
      Shunsuke Ogawa, Remi Nakashima, Mahmoud Kandeel, Yoshiaki Kitamura, Masato Ikeda, Yukio Kitade
    • 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] Synthesis and properties of modified siRNAs bearing 1,2-dideoxy-D-ribofuranose in their 3’-dangling end2013

    • Author(s)
      Yuki Nagaya, Kazumi Taniho, Ayaka Kobayashi, Mahoyo Mizoguchi, Yoshiaki Kitamura, Remi Nakashima, Masato Ikeda, Yukio Kitade
    • 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] Chemical modifications at the 3’-terminus of siRNA for suppressing off-target effects2013

    • Author(s)
      Remi Nakashima, Miwa Kawade, Yoshiaki Kitamura, Masato Ikeda, Yukio Kitade
    • 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] Stereoselective synthesis of 1-deoxy-1-ethynyl-β-D-ribofuranose and its applications2012

    • Author(s)
      枝吉佳奈
    • Organizer
      第39回国際核酸化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂(愛知県)
    • Year and Date
      2012-11-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Synthesis and biological properties of double-stranded RNAs containin g 1-deoxy-Dribofuranose2012

    • Author(s)
      小林彩花
    • Organizer
      第39回国際核酸化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂(愛知県)
    • Year and Date
      2012-11-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Synthesis of urea-substituted microRNAs possessing nuclease-resistance and their anticancer activities2012

    • Author(s)
      北出幸夫
    • Organizer
      第20回国際ヌクレオシド, ヌクレオチド, 核酸ラウンドテーブル
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2012-08-05
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] オリゴヌクレオチド誘導体及びそれを用いたオリゴヌクレオチド構築物並びに それらの製造方法2015

    • Inventor(s)
      北出 幸夫、柴田 綾
    • Industrial Property Rights Holder
      国立大学法人岐阜大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-060689
    • Filing Date
      2015-03-24
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] RNA干渉剤、その製造方法及びその利用2013

    • Inventor(s)
      北出幸夫 中島礼美
    • Industrial Property Rights Holder
      国立大学法人岐阜大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-29
    • Related Report
      2013 Annual Research Report
    • Overseas

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Published: 2012-04-24   Modified: 2019-07-29  

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