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Development of a two functional super catalytic antibody for the treatment of dementia

Research Project

Project/Area Number 18K05328
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionInstitute of Systems, Information Technologies and Nanotechnologies

Principal Investigator

Uda Taizo  公益財団法人九州先端科学技術研究所, マテリアルズ・オープン・ラボ, 特別研究員 (20232837)

Co-Investigator(Kenkyū-buntansha) 田口 博明  鈴鹿医療科学大学, 薬学部, 教授 (20549068)
一二三 恵美  大分大学, 全学研究推進機構, 教授 (90254606)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsbeta-amyloid / Tau protein / catalytic antibody / two functional / スーパー抗体酵素 / β-amyloid / Tauタンパク質 / 認知症 / scFv様分子 / 抗体酵素 / アミロイド / タウ蛋白
Outline of Final Research Achievements

This study is concerned with simultaneous decomposition of beta-amyloid (A-beta) and Tau protein (Tau). Firstly, we started to gain catalytic antibodies that can degrade A-beta and Tau. Safter that, genetically engineered scFv-like molecules in which their variable region portions were made by combining two molecules of the variable regions by a linker. Then, the FRET-antigens of A-beta and Tau were synthesized, and the degradation activity (peptidase activity) for these synthetic substrates was examined using the scFv-like molecule described above. As a result, it was found that this scFv-like molecule decomposes both antigens at the same time, achieving the intended purpose. Furthermore, when a mutation that deletes Pro95, which is present at the 95th position of this scFv-like molecule, was introduced, its enzymatic activity was improved by about 4 to 5 times, and the aggregation of beta-amyloid was completely blocked. This was a result that exceeded the intended plan.

Academic Significance and Societal Importance of the Research Achievements

本研究は、複数の抗原を同時に分解できる高性能分子を人為的に作製することを示した点において学術的に高く評価される。また、この新型機能を有する分子薬はこれまで世間には存在しなかったために将来の新型医薬品開発へと繋げる意味合いにおいて社会的に価値がある、と考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Discovery of Antibody Light Chains Possessing Tau Protein- Hydrolyzing Activity2020

    • Author(s)
      Hiroaki Taguchi, Yuki Kato, Taminao Ito, Emi Hifumi, and Taizo Uda
    • Journal Title

      Peptide science 2019

      Volume: 56 Pages: 139-140

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Journal Article] Discovery of antibody light chains capable of hydrolyzing tau protein using fluorescence-quenched substrate2019

    • Author(s)
      Hiroaki Taguchi, Iida Yuki, Mao Oba, Yoshio Fujita, Emi Hifumi, Taizo Uda
    • Journal Title

      Peptide science 2018

      Volume: 55 Pages: 40-40

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 2種類の抗原(Tau&Aβ)を同時分解する2機能型抗体酵素の作製と性質(II)2021

    • Author(s)
      宇田泰三、田口博明、野中玲実、 一二三恵美
    • Organizer
      第101春季日本化学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] タウタンパク質のリピート2部分を加水分解する抗体酵素の開発2020

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Presentation] 2種類の抗原(Tau&Aβ)を同時分解する2機能型抗体酵素の作製と性質2020

    • Author(s)
      宇田泰三、田口博明、一二三恵美
    • Organizer
      第100春季日本化学会年会
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Presentation] Unique antigenases to enzymatically cleave Tau peptides at C- and N-terminal moieties2019

    • Author(s)
      Taizo Uda, Hiroaki Taguchi, Emi Hifumi
    • Organizer
      The 12th ECCE(European Congress of Chemical Engineering) & 5th ECAB(European Congress of Applied Biotechnology)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Discovery of Antibody Light Chains Possessing Tau Protein- Hydrolyzing Activity2019

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] タウタンパク質を加水分解する抗体酵素の開発2019

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Tauペプチドを分解するヒト型抗体軽鎖2019

    • Author(s)
      宇田泰三・田口博明・一二三恵美
    • Organizer
      第99春季日本化学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Discovery of Antibody Light Chains Capable of Hydrolyzing Tau Protein Using Fluorescence-Quenched Substrate2018

    • Author(s)
      Hiroaki Taguchi, Iida Yuki, Mao Oba, Yoshio Fujita, Emi Hifumi, Taizo Uda
    • Organizer
      10th international peptide symposium
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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