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Construction of bispecific antibodies from the camelid antibody VHHs via in-cell protein trans-splicing

Research Project

Project/Area Number 26670051
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionYamagata University

Principal Investigator

Makabe Koki  山形大学, 理工学研究科, 准教授 (20508072)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords蛋白質工学 / 抗体工学 / 蛋白質トランススプライシング / 二重特異性抗体 / 重鎖抗体 / 抗体 / 蛋白質ライゲーション / インテイン
Outline of Final Research Achievements

Production of various combinations of bispecific antibodies (bsAbs) is important for evaluating the next generation antibody drugs. In spite of its importance, it requires several gene-engineering steps. Here, we report an alternative approach for bsAb construction to reduce the gene manipulation steps. We used a method to create bsAbs in vivo through protein trans-splicing. For proof-of-concept of this method, we show the construction of a bsAb with anti-epidermal growth factor receptor variable domain of heavy chain antibody (VHH) and anti-green fluorescent protein (GFP) VHH. We successfully constructed the bsAb using this method and the resulting bsAb has the bispecific activity.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Zinc ion-binding activity of an anti-ZnO VHH antibody, 4F22015

    • Author(s)
      Ryosuke Sasaki, Soichiro Kitazawa, Ryo Kitahara, Hikaru Nakazawa, Yoshikazu Tanaka, Izumi Kumagai, Mitsuo Umetsu, and Koki Makabe
    • Journal Title

      Chem. Lett.

      Volume: 44 Issue: 10 Pages: 1309-1311

    • DOI

      10.1246/cl.150537

    • NAID

      130005101454

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aromatic cluster mutations produce focal modulations of β-sheet structure.2015

    • Author(s)
      Biancalana M, Makabe K, Yan S, Koide S.
    • Journal Title

      Protein Sci.

      Volume: epub Issue: 5 Pages: 841-849

    • DOI

      10.1002/pro.2657

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Construction of a bispecific antibody via protein trans-splicing2015

    • Author(s)
      真壁幸樹
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Sheraton Waikiki (アメリカ合衆国)
    • Year and Date
      2015-12-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗酸化亜鉛VHH抗体の亜鉛イオン結合特性2015

    • Author(s)
      真壁幸樹
    • Organizer
      生物物理学会年会 2015
    • Place of Presentation
      金沢大学
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] βシートモデルタンパク質へのアミロイドコア配列の移植とその構造評価2015

    • Author(s)
      堀裕基、真壁幸樹
    • Organizer
      蛋白質科学会年会 2015
    • Place of Presentation
      徳島阿波銀ホール
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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