Development of novel chemogenetic tools for in vivo cell manipulation

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19109
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Nagoya Institute of Technology
• Principal Investigator: Tsukiji Shinya 名古屋工業大学, 工学(系)研究科(研究院), 教授 (40359659)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: ケモジェネティクス / in vivo / 局在スイッチ / 承認薬 / 局在性リガンド

Outline of Final Research Achievements

In this work, we aimed to develop new chemogenetic methods for controlling cell function in vivo. We pursued two approaches. In the first approach, we focused on engineering a drug-responsive localization-switching domain, which is localized in the cytoplasm in the absence of a drug but translocates to the inner leaflet of the plasma membrane in the presence of a drug. This project is still ongoing for further optimization. In the second approach, we applied our original "self-localizing ligand-induced protein translocation (SLIPT)" technique in vivo. We successfully developed a novel self-localizing ligand and protein tag pair that can be used to induce the plasma membrane recruitment of tag-fused proteins in cells within living mice. This tool may provide a powerful new platform for in vivo cell manipulation.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究は、生きた動物の体の中で細胞機能や細胞内情報伝達を自在に操作することを可能にする汎用的な化学遺伝学技術を開発するものである。このような技術は、動物個体内で進行する生命現象、細胞内／細胞間情報伝達、疾患などの制御機構を解明するための強力なin vivo生命研究ツールとなるばかりでなく、CAR-T細胞に代表されるような次世代医療や細胞医薬に資する革新的なin vivo細胞操作テクノロジーとしての展開が期待される。