2026-09-17 理化学研究所,産業技術総合研究所,九州大学
新たな停止スイッチAuxiCasp9と既存スイッチiCasp9の比較
＜関連情報＞
- https://www.riken.jp/press/2026/20260917_1/index.html
- https://pubs.acs.org/asbcd6/article/doi/10.1021/acssynbio.6c00010/5426555/Auxin-Activated-Caspase-9-System-AuxiCasp9-a
オーキシン活性化カスパーゼ9システム（AuxiCasp9）：遺伝子操作された細胞のための自殺スイッチ Auxin-Activated Caspase 9 System (AuxiCasp9), a Suicide Switch for Engineered Cells
Satoshi Yoshimoto;Shigeo S. Sugano;Shinya Sakuma;Yoko Yamanishi;Kosuke Dodo
ACS Synthetic Biology Published:September 08, 2026
DOI:https://doi.org/10.1021/acssynbio.6c00010
Abstract
Engineered cells incorporating synthetic gene circuits have been developed for therapeutic and diagnostic applications. However, cell proliferation and long-term engraftment may pose a risk of unpredictable toxicities. To address this issue, a suicide switch that can be selectively activated by exogenous stimuli has been developed as a regulatory system for engineered cells. However, the variety of reliable suicide switches is limited and insufficient for the orthogonal integration of multiple functions in engineered cells. This study developed auxin-activated caspase 9 (AuxiCasp9), a novel auxin-based suicide switch, by fusing the auxin receptor protein transport inhibitor response 1 (TIR1) carrying E7K/E10K/F74A mutations and auxin protein (Aux) to caspase 9. AuxiCasp9 exhibited cell death-inducing activity comparable to that of the established systems, inducible caspase 9 (iCasp9) and rapamycin-activated caspase 9 (RapaCasp9). Finally, we confirmed the orthogonality of AuxiCasp9 and iCasp9, suggesting the feasibility of multiplexed control of engineered cells.
