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Development of high-throughput screening methods for antisense oligonucleotides

Research Project

Project/Area Number 15K17886
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionTokyo University of Science

Principal Investigator

Hara Rintaro  東京理科大学, 薬学部生命創薬科学科, 助教 (70709766)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアンチセンス核酸医薬 / リボヌクレアーゼH(RNase H) / スクリーニング / カチオン性オリゴ糖 / カチオン性オリゴペプチド / RNase H / DNA/RNA二本鎖 / 核酸医薬 / ミスマッチ識別 / 水中での化学反応 / DNA-templated synthesis
Outline of Final Research Achievements

Antisense oligonucleotides (ASOs) are a promising candidate for nucleic acid drugs. In this study, we aimed to develop high-throughput screening methods in which high-active ASOs are chemically marked. Although we found some functional groups which have appropriate reactivity for these methods, we could not establish the efficient high-throughput screening method. On the other hand, I unintendedly found that some artificial cationic molecules could inhibit the cleavage reaction of mismatched RNAs by ASO and RNase H, which lead directly to side-effects of ASO-type drugs.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Artificial cationic oligosaccharides for heteroduplex oligonucleotide-type drugs2018

    • Author(s)
      Rintaro Iwata Hara, Yuki Hisada, Yusuke Maeda, Takanori Yokota, Takeshi Wada
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 4323-4323

    • DOI

      10.1038/s41598-018-22161-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of oligodiaminomannoses and analysis of their RNA duplex binding properties and their potential application as siRNA-based drugs2015

    • Author(s)
      Iwata, R; Doi, A.; Maeda, Y.; Wada, T.
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 13 Issue: 36 Pages: 9504-9515

    • DOI

      10.1039/c5ob01384d

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Improvement of single mismatch discrimination in RNase H cleavage by artificial cationic oligosaccharides2018

    • Author(s)
      Rintaro Hara, Takeshi Wada
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Synthesis and properties of L-2,4-diaminobutyric acid (Dab) oligomer-conjugated antisense oligonucleotides2018

    • Author(s)
      Taku Suenaga, Yusuke Maeda, Rintaro Hara, Takeshi Wada
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Taku Suenaga, Yusuke Maeda, Rintaro Hara, Takeshi Wada2017

    • Author(s)
      Synthesis and properties of L-2,4-diaminobutyric acid 8mer (Dab8)-conjugated antisense oligonucleotides
    • Organizer
      The 44th International Symposium on Nucleic Acids Chemistry
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 5位修飾ウラシルを含むホスホロチオエートDNAの立体選択的合成と性質評価2016

    • Author(s)
      吉野怜次郎、額賀陽平、岩田倫太朗、和田猛
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学京田辺キャンパス(京都)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 核酸医薬に結合する新規カチオン性人工ペプチドの合成と性質2016

    • Author(s)
      前田雄介、岩田倫太朗、坂本泰一、和田猛
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学京田辺キャンパス(京都)
    • Year and Date
      2016-03-25
    • Related Report
      2015 Research-status Report
  • [Presentation] RNA duplex binding molecules as carriers for siRNA2015

    • Author(s)
      Rintaro Iwata, Futoshi Nakayama, Sakie Hirochi, Kazuki Sato, Yusuke Maeda, Wenying Piao, Kazutaka Nishina, Takanori Yokota, Takeshi Wada
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015
    • Place of Presentation
      Sheraton Waikiki (Honolulu, Hawaii, USA)
    • Year and Date
      2015-12-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Artificial cationic oligosaccharides as carriers for nucleic acid drugs2015

    • Author(s)
      Rintaro Iwata, Yusuke Maeda, Taiichi Sakamoto, Takeshi Wada
    • Organizer
      The 42nd International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      イーグレ姫路()
    • Year and Date
      2015-09-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] 核酸医薬の創製と応用展開2016

    • Author(s)
      和田猛 他
    • Total Pages
      278
    • Publisher
      シーエムシー出版
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] RNAハイブリッド形成用核酸オリゴマー2016

    • Inventor(s)
      和田猛、吉野怜次郎、額賀陽平、原倫太朗
    • Industrial Property Rights Holder
      和田猛、吉野怜次郎、額賀陽平、原倫太朗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-046181
    • Filing Date
      2016-03-09
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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