Molecular design for in vivo delivery of antibodies targeting intracellular antigens

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H04794
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kyoto University
• Principal Investigator: Futaki Shiroh 京都大学, 化学研究所, 教授 (50199402)
• Co-Investigator(Kenkyū-buntansha): 樋口 ゆり子 京都大学, 薬学研究科, 教授 (40402797)
• Project Period (FY): 2021-04-05 – 2024-03-31
• Keywords: L17E / 抗体 / 細胞内送達 / 液滴 / コアセルベート

Outline of Final Research Achievements

Antibodies have the ability to recognize specific molecules in the body, and significant therapeutic benefits have been achieved by using antibodies as drugs that bind to disease-related proteins. Although there are many disease-related proteins in cells, antibodies cannot cross cell membranes, which hinders the development of antibody drugs. In this study, we demonstrated that (i) by mixing a chemically modified antibody with the multimers or polysaccharide conjugates of L17E, spherical complexes with a diameter of about 2 micrometers (coacervate) are formed, and (ii) a steep influx of the antibody into cells was observed by cellular contact of the coacervates.

Free Research Field

生体機能化学、細胞ペプチド工学

Academic Significance and Societal Importance of the Research Achievements

化学修飾した抗体とL17E等の細胞内導入ペプチドの多量体や架橋体がコアセルベートを形成し、高効率で細胞内に抗体を移送出来ることは、従来の概念では考えられなかった画期的な現象である。この移送を可能とするペプチドの物性や細胞側の要因を探ることで、抗体に限らず細胞内への導入が困難な種々の医薬品に適用可能な新しい細胞内送達法が開発への展開が期待される。