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Development of a novel approach toward nucleic acids-based therapeutics

Research Project

Project/Area Number 23659054
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

MINAKAWA Noriaki  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (40209820)

Co-Investigator(Kenkyū-buntansha) ITOH Koji  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (00184656)
YAMAZAKI Naoshi  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (20271083)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsゲノム創薬 / 核酸医薬 / U1 snRNA / 4'-チオ核酸 / 化学修飾核酸
Research Abstract

In this work, we aimed to prepare novel chemically modified RNA molecules possessing nuclease resistance and hybridization ability. In addition, we expected that these molecules exhibit editing ability of splicing abnormality. As a result, the resulting hybrid type of 4’-thionucleic acids showed preferable properties concerning of nuclease resistance and hybridization ability. Among the hybrid type of 4’-thionucleic acids developed, 2’-F-2’-thioRNA showed U1i activity arising from recruitment of U1 snRNA on pre-mRNA. Toward the end goal, we investigated the preparation of head-to-head oligonucleotides.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (12 results)

All 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect2012

    • Author(s)
      Mayumi Takahashi
    • Journal Title

      Nucleic Acids Research

      Volume: (in press) Issue: 12 Pages: 5787-5793

    • DOI

      10.1093/nar/gks204

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A practical post-modification synthesis of oligodeoxynucleotides containing 4,7-diaminoimidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside2012

    • Author(s)
      Noriko Tarashima, Yosuke Higuchi, Yasuo Komatsu, and Noriaki Minakawa
    • Journal Title

      Bioorg. Med. Chem

      Volume: 20 Issue: 24 Pages: 7095-7100

    • DOI

      10.1016/j.bmc.2012.10.035

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular stability of 2’-OMe-4’-thio...2012

    • Author(s)
      Mayumi Takahashi
    • Journal Title

      Nucleic Acids Reserch

      Volume: 40

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and characterization of oligodeoxynucleotides containing a novel tetraazabenzo[cd]azulene:naphthyridine base pair2011

    • Author(s)
      Yasuyuki Hirama, Noriaki Minakawa, and Akira Matsuda
    • Journal Title

      Bioorg. Med. Chem

      Volume: 19 Issue: 1 Pages: 352-358

    • DOI

      10.1016/j.bmc.2010.11.023

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] New imidazopyridopyrimidine : naphthyridine base-pairing motif, ImNN:NaOO, consisting of a DAAD:ADDA hydrogen bonding pattern, markedly stabilize DNA duplexes2011

    • Author(s)
      Kuramoto, K.
    • Journal Title

      Chem.Commun.

      Volume: 47 Issue: 38 Pages: 10818-10820

    • DOI

      10.1039/c1cc13805g

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Gene silencing by 2'-modified-4'-thio oligonucleotides via U1i machinery2012

    • Author(s)
      Yusaku Kikuchi, Naoshi Yamazaki, Yoshiharu Takiguchi, Noriaki Minakawa
    • 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、名古屋市
    • Related Report
      2012 Final Research Report
  • [Presentation] 2'-O-Me-4'-thioRNA as a Potential Use for Oligonucleotide Therapeutics2012

    • Author(s)
      A. Matsuda, M. Takahashi, N. Minakawa, H. Hatakeyama, M. Murata, Y. Sato, H. Harashima
    • Organizer
      8th Annual Meeting of the Oligonucleotide Therapeutic Society
    • Place of Presentation
      The conference center at Harvard Medical School, Boston, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] 2'-F-4'-チオヌクレオシドを含むキメラ型オリゴマーの合成と性質2012

    • Author(s)
      菊地優作、山崎尚志、滝口祥令、南川典昭
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学、札幌市
    • Related Report
      2012 Final Research Report
  • [Presentation] 改変U1snRNAによる遺伝子発現抑制2012

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会中国四国支部学術大会
    • Place of Presentation
      島根県民会館(島根県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gene silencing by 2'-modified-4'-thio oligonucleotides via U1i machinery2012

    • Author(s)
      南川典昭
    • 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)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 2’-F-4’-チオヌクレオシドを含むキメラ型オリゴマーの合成と性質2012

    • Author(s)
      菊地優作
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.tokushima-u.ac.jp/ph/faculty/labo/mar/

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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