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Development of lecithin-modified therapeutic proteins as biobetters

Research Project

Project/Area Number 17K01395
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNihon University

Principal Investigator

Ishihara Tsutomu  日本大学, 工学部, 教授 (70349554)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsバイオベター / レシチン / DDS / 抗体 / バイオ医薬 / 酵素 / 化学修飾 / タンパク医薬 / ドラッグデリバリー
Outline of Final Research Achievements

We have attempted to develop lecithin-modified proteins as improved therapeutic proteins (biobetters). Lysosome enzyme or IgG antibody was used as the protein, and its activity and interaction with cultured cells were analyzed. The lecithinized lysosomal enzyme had low cytotoxicity and formed a complex with plasma proteins. Furthermore, the enzyme was internalized in the cells, and showed high enzymatic activity. On the other hand, it was found that the lecithinized antibody can maintain the antigen-binding activity by reducing the amount of organic solvent during the synthetic reaction. This lecithinized antibody was more internalized in the cells than the unmodified antibody.

Academic Significance and Societal Importance of the Research Achievements

タンパク質を有効成分とするバイオ医薬の開発は近年劇的に進展しており、今後の薬物療法の主流となることは疑いない。しかし、タンパク質の生物活性の強さと実際の薬理効果は必ずしも相関せず、その活性を最大限に引き出すには、体内動態を制御することが求められる。本研究では、レシチン修飾という基幹技術により、活性を維持しつつタンパク質の細胞内への移行性を高められることを明らかにした。この成果は、バイオ医薬の有用性を飛躍的に拡大できる可能性を秘める。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Development of liver-specific ribavirin-loaded nanoparticles with reduced cytotoxicity2017

    • Author(s)
      Kaneko K, Ishihara T.
    • Journal Title

      Cogent Medicine

      Volume: 4 Issue: 1 Pages: 1418133-1418133

    • DOI

      10.1080/2331205x.2017.1418133

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alkyne-functionalized cationic polysiloxane polymers conjugated with targeting molecules by click reactions for DNA delivery2017

    • Author(s)
      Kihara Y, Maeda R, Imaizumi A, Ichikawa T, Nemoto N, Ishihara T, Hirano N, and Haruki M.
    • Journal Title

      J. Nanosci. Nanotechnol.

      Volume: 17 Issue: 7 Pages: 5081-5089

    • DOI

      10.1166/jnn.2017.13121

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] ホスファチジルコリンを化学修飾したタンパク質の合成とその活性評価2019

    • Author(s)
      宗方泉稀、松本安平、星貴也、澁井美咲、石原務
    • Organizer
      2019年度化学系学協会東北大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ホスファチジルコリンを化学修飾したタンパク質の合成とその活性評価2018

    • Author(s)
      松本安平、星貴也、澁井美咲、水島徹、石原務
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2024-12-25  

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