Mechanism of cell-penetration of an artificial coiled-coil protein carrier having high structure anisotropy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 28040:Nanobioscience-related
• Research Institution: Nippon Institute of Technology
• Principal Investigator: Sano Ken-Ichi 日本工業大学, 基幹工学部, 教授 (80321769)
• Co-Investigator(Kenkyū-buntansha): 池添 泰弘 日本工業大学, 基幹工学部, 教授 (70334315)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞内デリバリー / コイルドコイル構造 / ナノ構造

Outline of Final Research Achievements

Efficient delivery of proteins and peptides into cancer cells are investigated, and tried to apply it to treatment. However, previously investigated drug delivery carriers for cell-penetration did not show enough efficiency for intracellular delivery, which restrict the use of cancer therapy. In a previous study, we have created an artificial protein cell-penetrating carrier, and its cell-penetrating activity shows ~ 1000 times greater than that of previously reported carriers. In this study, we have investigated that the mechanism of the superior cellular internalization of the artificial protein carrier. As a result, it is revealed that the behavior of the artificial protein carrier cell-penetration based on the structural properties of the molecule differs from that of previously reported carriers, and also cleared that the efficiency of the binding and activation of cell-penetration activity of the artificial protein is much greater than that of previously reported carriers.

Free Research Field

生体分子工学

Academic Significance and Societal Importance of the Research Achievements

この研究成果により、細胞透過人工タンパク質が、従来から知られている細胞表面にある糖鎖だけでなく、別の糖鎖へ強く結合し、その結果、細胞内への導入を効率よく誘導できることが明らかになった。さらに、人工タンパク質の細胞表面への結合そのものによって生じる細胞膜への力学的なストレスが、細胞内への導入に大きく関与していることを示したことは、応用利用だけでなく、基礎科学における新たな知見を与えた。これらの知見は、細胞内への運び屋の新たな設計指針を与えるものである。