• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Construction of novel nucleic acid threaded structures and their application to mRNA protection methods

Research Project

Project/Area Number 21K19323
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionTohoku University

Principal Investigator

Onizuka Kazumitsu  東北大学, 多元物質科学研究所, 准教授 (00707961)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsRNA / 貫通構造体 / ロタキサン / カテナン / フリップアウト / 翻訳 / DNA / 環状核酸 / 核酸 / 環状化 / 機能性核酸 / mRNA
Outline of Research at the Start

ユニークな構造や性質を持つロタキサンをキーワードとした研究は数多く行われている一方で、ロタキサン様構造構築の難しさのため、生命科学分野への応用に関しては十分に開拓できておらず、更なるブレイクスルーが必要とされている。本研究では独自の研究で見出した標的核酸塩基のフリップアウトを誘起する機能性核酸を利用し、これまで実現されたことのない小さな環を持つ核酸貫通構造体(ロタキサン様構造)の簡便な構築を目指す。さらにこの非共有結合性修飾により、天然のRNAに望みの機能を追加できる汎用的なプラットフォームの構築、特に末端保護によるmRNA安定化、翻訳効率の向上を目標に研究を行う。

Outline of Final Research Achievements

In this study, we have started research using functional nucleic acids with flip-out ability to construct new nucleic acid-treading structures and explore their functions, with a particular aim to control translation reactions. Although the initially designed molecule showed flip-out ability, it did not result in the formation of a threaded structure. Based on previous findings, we attempted to form a threaded structure into the target RNA by the slipping of a cyclized nucleic acid with tails. We improved the synthesis method and attempted to control translation using newly synthesized cyclized nucleic acids, but no significant change in efficiency was observed. We have succeeded in elucidating the detailed mechanism of formation of the threading structures (pseudorotaxanes and catenanes) and in non-covalent labeling, it is expected that the functionality will be further improved in the future.

Academic Significance and Societal Importance of the Research Achievements

ロタキサンのような貫通構造体の生化学分野への応用に関しては未だ課題が多く、更なるブレイクスルーが必要とされている。環状形態が作り出す貫通構造は分子認識・機能発現にとって理想的な場を構築するため、生体分子に対する機能を備えた貫通構造体形成分子の創製は学術的に価値ある挑戦である。本研究の最終的な成果として、RNAに貫通構造体を形成させることで、共有結合を介さずに効率的に修飾やラベル化が可能になる技術を確立することに成功した。直鎖のRNAだけでなく環状RNAでも同様の修飾を可能にした。これは環状RNAが関与する新たな生命現象の発見・解明やその機能制御に資する生化学ツールとしての応用が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (25 results)

All 2024 2023 2022 2021 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (16 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Creation of Unique Nucleic Acid Structures Using Nucleic Acid Reaction Fields2023

    • Author(s)
      Onizuka Kazumitsu
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 81 Issue: 8 Pages: 809-816

    • DOI

      10.5059/yukigoseikyokaishi.81.809

    • ISSN
      0037-9980, 1883-6526
    • Year and Date
      2023-08-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topological capture of mRNA for silencing gene expression2023

    • Author(s)
      Lyu Fangjie、Tomita Takashi、Abe Naoko、Hiraoka Haruka、Hashiya Fumitaka、Nakashima Yuko、Kajihara Shiryu、Tomoike Fumiaki、Shu Zhaoma、Onizuka Kazumitsu、Kimura Yasuaki、Abe Hiroshi
    • Journal Title

      Chemical Communications

      Volume: 59 Issue: 77 Pages: 11564-11567

    • DOI

      10.1039/d2cc06189a

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of Direction-Controllable Pseudorotaxane and Catenane Using Chemically Cyclized Oligodeoxynucleotides and Their Noncovalent RNA Labeling2023

    • Author(s)
      Kuwahara Kazuki、Yajima Sayaka、Yamano Yuuhei、Nagatsugi Fumi、Onizuka Kazumitsu
    • Journal Title

      Bioconjugate Chemistry

      Volume: - Pages: 696-706

    • DOI

      10.1021/acs.bioconjchem.3c00031

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hybridization-specific chemical reactions to create interstrand crosslinking and threaded structures of nucleic acids2022

    • Author(s)
      Onizuka Kazumitsu、Yamano Yuuhei、Abdelhady Ahmed Mostafa、Nagatsugi Fumi
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 20 Issue: 23 Pages: 4699-4708

    • DOI

      10.1039/d2ob00551d

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Photochemical Labeling of Nucleic Acid by Photocatalyst Tethered DNA Probe2022

    • Author(s)
      Yamano Yuuhei、Onizuka Kazumitsu、Sasaki Madoka、Sato Shinichi、Nagatsugi Fumi
    • Journal Title

      Chemistry Letters

      Volume: 51 Issue: 12 Pages: 1121-1124

    • DOI

      10.1246/cl.220397

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid Alkene-Alkene Photo-Cross-Linking on the Base-Flipping-Out Field in Duplex DNA2022

    • Author(s)
      Abdelhady Ahmed Mostafa、Onizuka Kazumitsu、Ishida Kei、Yajima Sayaka、Mano Eriko、Nagatsugi Fumi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 87 Issue: 5 Pages: 2267-2276

    • DOI

      10.1021/acs.joc.1c01498

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Pseudorotaxane formation by cyclized oligo DNAs and approach to accelerating its formation2024

    • Author(s)
      Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi
    • Organizer
      日本化学会第104春季年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 擬ロタキサンの貫通方向制御能とカテナン形成能を有する新規環状化核酸の開発2023

    • Author(s)
      桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史
    • Organizer
      日本ケミカルバイオロジー学会 第17回年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 新規環状化核酸による擬ロタキサン形成メカニズムの解明とカテナン形成への展開2023

    • Author(s)
      桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史
    • Organizer
      第20回 ホスト-ゲスト・超分子化学シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] RNA標的創薬を指向した核酸化学ツール開発2023

    • Author(s)
      鬼塚和光
    • Organizer
      令和5年度日本薬学会東北支部主催 第21回化学系若手研究者セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Formation of pseudorotaxane and catenane structures using novel cyclized oligodeoxynucleotides2023

    • Author(s)
      Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi
    • Organizer
      ISNAC2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Creation of base flipping-out structures on DNA and RNA using carbazole-modified thymidine analogs2023

    • Author(s)
      Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Madoka Sasaki, Ahmed Mostafa Abdelhady, Kei Ishida, Fumi Nagatsugi
    • Organizer
      ISNAC2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 化学修飾機能性オリゴ核酸の開発研究2022

    • Author(s)
      鬼塚和光
    • Organizer
      日本核酸医薬学会 第7回年会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Development of novel threaded structure-forming nucleic acids with the ability of slipping direction control and their mechanism elucidation2022

    • Author(s)
      Kazuki Kuwahara, Kazumitsu Onizuka, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi
    • Organizer
      令和4年度化学系学協会東北大会
    • Related Report
      2022 Research-status Report
  • [Presentation] スリッピング方向が制御可能な貫通構造形成核酸の開発とそのメカニズム解明2022

    • Author(s)
      桑原和貴, 鬼塚和光, 矢島さやか, 山野雄平, 永次史
    • Organizer
      第12回 CSJ化学フェスタ2022
    • Related Report
      2022 Research-status Report
  • [Presentation] Nucleic acids modification by photo-catalytic reaction2022

    • Author(s)
      Yuuhei Yamano, Kazumitsu Onizuka, Madoka Sasaki, Shinichi Sato, Fumi Nagatsugi
    • Organizer
      ISNAC2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pseudorotaxane and catenane formation via the slipping process2022

    • Author(s)
      Kazumitsu Onizuka, Kazuki Kuwahara, Sayaka Yajima, Yuuhei Yamano, Fumi Nagatsugi
    • Organizer
      ISNAC2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Selective photo-labeling of G4 DNA-binding protein2022

    • Author(s)
      Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Shinichi Sato, Tatsuki Masuzawa, Takanori Oyoshi, Fumi Nagatsugi
    • Organizer
      日本化学会 第102春季年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Chemical reactions for nucleic acids research2021

    • Author(s)
      Kazumitsu Onizuka
    • Organizer
      Current Topics in Emergent Materials and Devices-Cooperated with Advanced Research Network in Materials and Devices in Japan 5-Star Alliance, CEFMS-NYCU
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Efficient alkene-alkene photo-cross-linking reaction on the flipping-out field in duplex DNA2021

    • Author(s)
      Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Sayaka Yajima, Kei Ishida, Eriko Mano, Fumi Nagatsugi
    • Organizer
      FIBER日本核酸化学会若手フォーラム
    • Related Report
      2021 Research-status Report
  • [Presentation] Efficient cross-linking reaction using base flip-inducing oligodeoxynucleotides2021

    • Author(s)
      Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Sayaka Yajima, Kei Ishida, Eriko Mano, Fumi Nagatsugi
    • Organizer
      IS3NA-IRT 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Creation of interstrand cross-linked nucleic acids and their application for miRNA inhibition2021

    • Author(s)
      Ahmed Mostafa Abdelhady, Kazumitsu Onizuka, Yu Hirano, Komatsu, Fumi Nagatsugi
    • Organizer
      ISNAC2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Remarks] 永次研究室HP

    • URL

      https://www2.tagen.tohoku.ac.jp/lab/nagatsugi/html/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 環状構造にRNAが貫通する機能性核酸を開発 -分子機械創製やRNAの機能化法への展開に期待-

    • URL

      http://www2.tagen.tohoku.ac.jp/lab/news_press/20230327/

    • Related Report
      2022 Research-status Report
  • [Remarks] 永次研究室ホームページ

    • URL

      http://www2.tagen.tohoku.ac.jp/lab/nagatsugi/html/index.html

    • Related Report
      2022 Research-status Report 2021 Research-status Report

URL: 

Published: 2021-07-13   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi