Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases. However, concerns over the safety and efficacy require to be further addressed in order to realize their full potential. Synthetic receptors, a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules, have been rapidly developed and applied as a powerful solution. Delicately designed and engineered, they can be applied to finetune the therapeutic activities, i.e., to regulate production of dosed, bioactive payloads by sensing and processing user-defined signals or biomarkers. This review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical research. With a special focus on four synthetic receptor systems at the forefront, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, we address the generalized strategies to design, construct and improve synthetic receptors. Meanwhile, we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

细胞和基因疗法为治疗一系列难以治疗的疾病带来了巨大的希望。然而，为了充分发挥其潜力，需要进一步解决对安全性和有效性的担忧。合成受体是一种能够精确控制治疗细胞和遗传模块功能的合成生物学工具，作为一种强大的解决方案得到了迅速的开发和应用。经过精心设计和工程设计，它们可用于微调治疗活动，即通过感测和处理用户定义的信号或生物标志物来调节剂量的生物活性有效负载的产生。这篇综述概述了用于重编程治疗细胞的多种合成受体系统及其在生物医学研究中的广泛应用。我们特别关注四种最前沿的合成受体系统，包括嵌合抗原受体 (CAR) 和合成 Notch (synNotch) 受体，提出了设计、构建和改进合成受体的通用策略。同时，我们还强调了合成受体系统治疗应用不断扩大的前景以及当前临床转化的挑战。