Department of Laboratory Medicine, The First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Center for Cross-disciplinary Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, P.R. China.
Department of Laboratory Medicine, The First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Center for Cross-disciplinary Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, P.R. China.
Cell Rep. 2023 Apr 25;42(4):112385. doi: 10.1016/j.celrep.2023.112385. Epub 2023 Apr 11.
Implementation of designer receptors in engineered cells confers them to sense a particular physiological or disease state and respond with user-defined programs. To expand the therapeutic application scope of engineered cells, synthetic receptors realized through different strategies are in great demand. Here, we develop a synthetic receptor system that exerts dual control by incorporating two transmembrane helices for the signal chain. Together with a sensor-actuator device with minimal background signals and a positive loop circuit, this receptor system can sensitively respond to extracellular protein signals. We demonstrate that this synthetic receptor system can be readily adapted to respond to various inputs, such as interleukin-1 (IL-1), programmed death ligand 1 (PD-L1), and HER2, and release customized outputs, including fluorescence signals and the therapeutic molecule IL-2. The robust signaling ability and generality of this receptor system promise it to be a useful tool in the field of cell engineering for fundamental research and translational applications.
在工程细胞中实现设计受体使它们能够感知特定的生理或疾病状态，并根据用户定义的程序做出响应。为了扩大工程细胞的治疗应用范围，人们迫切需要通过不同策略实现的合成受体。在这里，我们开发了一种合成受体系统，该系统通过包含两个跨膜螺旋的信号链来进行双重控制。该受体系统与具有最小背景信号的传感器-执行器装置和正环电路一起，可以灵敏地响应细胞外蛋白信号。我们证明，这种合成受体系统可以很容易地适应各种输入，如白细胞介素-1（IL-1）、程序性死亡配体 1（PD-L1）和 HER2，并释放定制的输出，包括荧光信号和治疗分子 IL-2。该受体系统强大的信号能力和通用性使其有望成为细胞工程领域基础研究和转化应用的有用工具。
