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Exploration of optimized chemical structure of siRNA based on the functional structure of human argonaute 2 protein

Research Project

Project/Area Number 25410182
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionKinki University

Principal Investigator

FUJII Masayuki  近畿大学, 工学部, 教授 (60199297)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords核酸化学 / 遺伝子サイレンシング / 化学修飾siRNA / アルゴノート2 / 核酸医薬 / オフターゲット効果 / 核酸関連化学 / アルゴノート2 / 遺伝子デリバリー
Outline of Final Research Achievements

In the present study, we could demonstrate that chemical modification of siRNA increased the probability of the selection of antisense strand by Ago2, that conjugation of siRNA with signal peptides made it possible to control the intracellular localization of siRNA, and that non-covalent complexation of siRNA with the designed amphiphilic peptide improved cellular uptake and biological stability of siRNA. By a combination of further chemical modification, conjugation and complexation with a variety of functional molecules, we believe we can design an optimized structure of siRNA therapeutics which can effectively penetrate into cells and bind to the target molecule with a good affinity and specificity, without any side effects.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (22 results) (of which Int'l Joint Research: 5 results) Book (3 results)

  • [Journal Article] 核酸医薬の分子デザイン;化学修飾、コンジュゲート、複合体2016

    • Author(s)
      藤井政幸
    • Journal Title

      Med Chem News

      Volume: 26 Pages: 22-28

    • NAID

      130007388030

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 核酸医薬における生物学的分子基盤と核酸分子設計2015

    • Author(s)
      藤井政幸
    • Journal Title

      日本核酸医薬学会会報

      Volume: 19 Pages: 7-7

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Journal Article] Rational Design of siRNA by Chemical Modification and Conjugation2015

    • Author(s)
      ③Yasuhiro Shinkai, Yu Ohno, Hirohumi Fujii, Kanami Akaike, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Journal Title

      Proceeding of the 11th Oligonucleotide Therapeutic Society Annual Meeting

      Volume: 2015 Pages: 138-138

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synthesis, purification and delivery into mammalian cells of phosphoryl guanidine oligonucleotides (PGO) with either DNA or 2'-OMe RNA backbone2015

    • Author(s)
      ④Aleksey I. Vladyko, Boris P. Chelobanov, Maxim S. Kupryushkin, Dmitrii V. Pyshnyi, Masayuki Fujii and Dmitry A. Stetsenko
    • Journal Title

      Proceedings of the 42nd International Symposium of Nucleic Acid Chemistry

      Volume: 2015 Pages: 244-245

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gene Silencing by Chemically Modified siRNAs Bearing Cationic Charge on 5’-End2015

    • Author(s)
      ⑤Yu Ohno, Kanami Akaike, Yasuhiro Shinkai, Hirohumi Fujii, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Journal Title

      Proceedings of the 42nd International Symposium of Nucleic Acid Chemistry

      Volume: 2015 Pages: 322-323

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gene Silencing by miRNA-like siRNAs Bearing Mismatches and Bulges2015

    • Author(s)
      ⑥Yasuhiro Shinkai, Hirohumi Fujii, Yu Ohno, Kanami Akaike, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Journal Title

      Proceedings of the 42nd International Symposium of Nucleic Acid Chemistry

      Volume: 2015 Pages: 324-325

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bioconjugation of oligodeoxynucleotides carrying 1,4-dicarbonyl groups via reductive amination with lysine residues2015

    • Author(s)
      B. Yang, A. Jinnouchi, K. Usui, T. Katayama, M. Fujii, H. Suemune, M. Aso
    • Journal Title

      Bioconjugate Chemistry

      Volume: 26 Issue: 8 Pages: 1830-1838

    • DOI

      10.1021/acs.bioconjchem.5b00361

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Non-Toxic Delivery and Gene Silencing by siRNA-Peptide Complex2013

    • Author(s)
      Ayumi Takashina, Jyunichi Obata, Shutaro Fujiaki and Masayuki Fujii
    • Journal Title

      Peptide Science

      Volume: 100 Pages: 92-93

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conformational changes of the phenyl and naphthyl isocyanate-DNA adducts2013

    • Author(s)
      S. Nakano, Y. Uotani, Y. Sato, H. Oka, M. Fujii, and N. Sugimoto
    • Journal Title

      Nucleic Acids Res.

      Volume: 41 Issue: 18 Pages: 8581-8590

    • DOI

      10.1093/nar/gkt608

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 5’-アミノTを有するsiRNAの遺伝子サイレンシング効果2015

    • Author(s)
      ④大野結有、新貝恭広、藤井啓史、柏原慎一、苗村円佳、神武洋二郎、山吉麻子、村上章、藤井政幸
    • 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
    • Int'l Joint Research
  • [Presentation] ミスマッチまたはバルジ構造を有するmiRNA様siRNAの遺伝子サイレンシング効果2015

    • Author(s)
      ⑤新貝恭広、藤井啓史、柏原慎一、苗村円佳、神武洋二郎、山吉麻子、村上章、藤井政幸
    • 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
    • Int'l Joint Research
  • [Presentation] Gene Silencing by Chemically Modified siRNAs Bearing Cationic Charge on 5’-End2015

    • Author(s)
      Yu Ohno, Kanami Akaike, Yasuhiro Shinkai, Hirohumi Fujii, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Organizer
      第42回国際核酸化学シンポジウム
    • Place of Presentation
      イーグルひめじあいめっせホール(姫路市)
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gene Silencing by miRNA-like siRNAs Bearing Mismatches and Bulges2015

    • Author(s)
      ②Yasuhiro Shinkai, Hirohumi Fujii, Yu Ohno, Kanami Akaike, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Organizer
      第42回国際核酸化学シンポジウム
    • Place of Presentation
      イーグルひめじあいめっせホール(姫路市)
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rational Design of siRNA by Chemical Modification and Conjugation2015

    • Author(s)
      ③Yasuhiro Shinkai, Yu Ohno, Hirohumi Fujii, Kanami Akaike, Ayumi Takashina, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Organizer
      11th Oligonucleotide Therapeutic Society Annual Meeting
    • Place of Presentation
      オランダ(ライデン市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カチオン修飾siRNAによる遺伝子サイレンシング効果2015

    • Author(s)
      藤井 政幸・高科あゆみ・苗村円佳・神武洋二郎・山吉麻子・有吉純平・村上章
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      日本大学船橋キャンパス(千葉県舟橋市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Presentation] GENE SILENCING BY CATIONIC SIRNA2014

    • Author(s)
      Ayumi Takashina, Hikari Kayano, Tomohiro Emi, Madoka Naemura, Yojiro Kotake, Jumpei Ariyoshi, Asako Yamayoshi, Akira Murakami and Masayuki Fujii
    • Organizer
      The 41st International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] EFFICIENT TRANSFECTION OF SIRNA BY DESIGNED PEPTIDES2014

    • Author(s)
      Hikari Kayano, Ayumi Takashina, Madoka Naemura, Yojiro Kotake, Yasutaka Morita and Masayuki Fujii
    • Organizer
      The 41st International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] siRNA-ペプチド複合体の細胞内導入と遺伝子サイレンシング効果2014

    • Author(s)
      萱野光、苗村円佳、高科あゆみ、神武洋二郎、森田資隆、藤井政幸
    • Organizer
      第4回CSJ化学フェスタ2014
    • Place of Presentation
      タワーホール舟堀(東京都江戸川区)
    • Year and Date
      2014-10-14 – 2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] カチオン性siRNAの遺伝子サイレンシング効果2014

    • Author(s)
      高科あゆみ、萱野光、江見友裕、苗村円佳、神武洋二郎、有吉純平、山吉麻子、村上章、藤井政幸
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2014
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2014-09-08 – 2014-09-09
    • Related Report
      2014 Research-status Report
  • [Presentation] CATIONIC CHARGE ON SIRNA AND RNAI EFFECT2014

    • Author(s)
      Ayumi Takashina, Hikari Kayano, Tomohiro Emi, Kana Murakami, Noriko Ogawa, Jumpei Ariyoshi, Asako Yamayoshi and Masayuki Fujii
    • Organizer
      XXI Round Table on Chemical Biology of Nucleic Acids
    • Place of Presentation
      ポズナン大学(ポーランド、ポズナン)
    • Year and Date
      2014-08-24 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] Synthesis and Gene Silencing by siRNA-Peptide Conjugates2014

    • Author(s)
      Ayumi Takashina, Tomoniro Emi, Hikaru Kayano and Masayuki Fujii
    • Organizer
      EMBO Conference, Chemical Biology 2014
    • Place of Presentation
      ハイデルベルグEMBL(ドイツ、ヘイデルベルグ市)
    • Year and Date
      2014-08-20 – 2014-08-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 核酸コンジュゲートの新規固相フラグメント縮合法2014

    • Author(s)
      江見友裕、鶴岡昂洋、藤井政幸
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] カチオン電荷を有するsiRNAのサイレンシング効果2014

    • Author(s)
      高科あゆみ、藤井政幸
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 5'-末端修飾siRNAの遺伝子サイレンシング効果2014

    • Author(s)
      鶴岡昂洋、萱野光、江見友裕、高科あゆみ、藤井政幸
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 萱野光、鶴岡昂洋、江見友裕、高科あゆみ、藤井政幸2014

    • Author(s)
      新規両親媒性ペプチドコンジュゲートによるsiRNAの細胞内導入と遺伝子サイレンシング効果
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Non-Toxic Delivery and Gene Silencing by siRNA-Peptide Complex2013

    • Author(s)
      Ayumi Takashina, Jyunichi Obata, Shutaro Fujiaki and Masayuki Fujii
    • Organizer
      23rd American Peptide Symposium
    • Place of Presentation
      ヒルトンワイコロワホテル(アメリカ、ハワイ州、ワイコロワ)
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規ペプチドによるsiRNAの無毒性細胞導入と遺伝子サイレンシング2013

    • Author(s)
      藤井政幸、高科あゆみ、小幡淳一、藤明修太郎
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都テルサ(京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Chemical modification of siRNAs and their silencing effects2013

    • Author(s)
      Masayuki Fujii and Ayumi Takashina
    • Organizer
      9th Annual Meeting of the Oligonucleotide Therapeutics Society
    • Place of Presentation
      ロイヤルコンチネンタルホテル(イタリア、ナポリ市)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトアルゴノート2タンパクの機能構造と化学修飾siRNAのサイレンシング効果2013

    • Author(s)
      高科あゆみ・藤井政幸
    • Organizer
      CSJ化学フェスタ2013
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Related Report
      2013 Research-status Report
  • [Presentation] Structure of Human Argonaute2 Protein and Chemically Modified siRNA2013

    • Author(s)
      Ayumi Takashina and Masayuki Fujii
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] ハイブリッドペプチドによるsiRNAの無毒性細胞内デリバリーと遺伝子サイレンシング

    • Author(s)
      小幡 淳一、高科 あゆみ、藤明 修太郎、藤井 政幸
    • Organizer
      遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      帝京大学板橋キャンパス(東京都板橋区)
    • Related Report
      2013 Research-status Report
  • [Book] 核酸医薬の創製と応用展開第III編 DDS 第6章 新規ペプチドによるsiRNAの無毒性細胞導入2016

    • Author(s)
      藤井政幸
    • Publisher
      ㈱シーエムシー出版
    • Related Report
      2015 Annual Research Report
  • [Book] 遺伝子治療・診断の最先端技術と新しい医薬品・診断薬の開発2014

    • Author(s)
      藤井政幸、高科あゆみ、神武洋二郎、森田資隆、山田康枝
    • Total Pages
      566
    • Publisher
      (株)技術情報協会
    • Related Report
      2014 Research-status Report
  • [Book] 第4版マクマリー・生物有機化学(共訳)2014

    • Author(s)
      藤井政幸 他6名
    • Total Pages
      375
    • Publisher
      丸善
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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