Development of lecithin-modified therapeutic proteins as biobetters

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K01395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Nihon University
• Principal Investigator: Ishihara Tsutomu 日本大学, 工学部, 教授 (70349554)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: バイオベター / レシチン / ＤＤＳ

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.

Free Research Field

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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。