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Regulation of cell differentiation signal with oligonucleotide-based growth factor mimetics

Research Project

Project/Area Number 17K14512
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

UEKI Ryosuke  東京大学, 大学院工学系研究科(工学部), 助教 (90755703)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsDNAアプタマー / 受容体 / 増殖因子 / 核酸アプタマー / 受容体シグナル / アプタマー / 幹細胞 / 細胞シグナル / 分化誘導
Outline of Final Research Achievements

Fibroblast growth factor (bFGF) is widely used as an essential factor for maintaining and proliferating stem cells in an undifferentiated state, and is one of the most important growth factors in the current field of regenerative medicine. On the other hand, synthetic alternatives to bFGF have been highly sought after due to its low thermal stability.
In this study, we developed functional mimetics of bFGF based on oligonucleotide. Focusing on the mechanism by which FGF induces intracellular signal by dimerizing the receptor, several dimer forms of DNA aptamers that bind to the FGF receptor were synthesized.

Academic Significance and Societal Importance of the Research Achievements

近年の再生医療分野において、細胞の分化・増殖を制御する増殖因子に大きな注目が寄せられている。特に、iPS細胞の培養、および特定の体細胞への分化誘導プロセスにおいて必須の因子として汎用されている。しかし、天然タンパク質である増殖因子の製造には動物細胞による発現系を要するため、製造コストと品質管理の観点から、その大量供給に大きなハードルが課されている。本研究では、増殖因子の機能を模倣し、細胞の分化シグナルを制御可能な「増殖因子ミメティクス」を開発するための分子設計指針を探る。特に、化学合成可能なDNAを用いて、従来の増殖因子の欠点を克服する有望な代替化合物の開発へ繋げることを目指す。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] DNA Aptamer Assemblies as Fibroblast Growth Factor Mimics and Their Application in Stem Cell Culture2019

    • Author(s)
      3.Ryosuke Ueki*, Saki Atsuta, Ayaka Ueki, Junya Hoshiyama, Jingyue Li, Yohei Hayashi, Shinsuke Sando*
    • Journal Title

      Chem. Commun.

      Volume: 55 Issue: 18 Pages: 2672-2675

    • DOI

      10.1039/c8cc08080a

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 増殖因子ミメティクス核酸 再生医療応用と化学ツールとしての展開2019

    • Author(s)
      植木 亮介
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 増殖因子ミメティクス核酸による細胞シグナル制御2018

    • Author(s)
      植木 亮介、秋山 桃子、藤井 雅史、黒田 真也、山東 信介
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nano-chemical tools for controlling dynamic assembly of cell membrane receptors2017

    • Author(s)
      Ryosuke Ueki, Naoto kanda, Shinsuke Sando
    • Organizer
      The 2nd International Symposium on Biofunctional Chemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel DNA aptamer assemblies that control growth factor signaling and cellular functions2017

    • Author(s)
      Ryosuke Ueki, Saki Atsuta, Ayaka Utsumi, Yohei Hayashi, Shinsuke Sando
    • Organizer
      The 44th International Symposium on Nucleic Acids Chemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of therapeutic potential of oligonucleotide-based growth factor mimetics2017

    • Author(s)
      Ryosuke Ueki, Satoshi Uchida, Naoto Kanda, Horacio Cabral, Shinsuke Sando
    • Organizer
      Nucleosides, Nucleotides & Oligonucleotides Gordon Research Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] In vitro selection of DNA aptamers to a growth factor receptor and their characterization2017

    • Author(s)
      Saki Atsuta, Ryosuke Ueki, Ayaka Utsumi, Yohei Hayashi, Shinsuke Sando
    • Organizer
      The 44th International Symposium on Nucleic Acids Chemistry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 核酸アプタマーの最前線2019

    • Author(s)
      星山純也, 植木亮介, 山東信介
    • Total Pages
      4
    • Publisher
      ニューサイエンス社
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] FUNCTIONAL MIMETICS OF FIBROBLAST GROWTH FACTOR COMPRISED OF NUCLEIC ACID2018

    • Inventor(s)
      山東信介、植木亮介、植木彩香、熱田早紀
    • Industrial Property Rights Holder
      山東信介、植木亮介、植木彩香、熱田早紀
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2017-04-28   Modified: 2021-02-19  

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