University of Chinese Academy of Sciences, Beijing, 101408, China.
State Key Laboratory of Stem Cell and Regenerative Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Signal Transduct Target Ther. 2024 Jan 3;9(1):7. doi: 10.1038/s41392-023-01680-5.
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.
细胞和基因疗法在治疗一系列难治性疾病方面具有巨大的潜力。然而，为了充分发挥其潜力，需要进一步解决安全性和有效性方面的担忧。合成受体是一种合成生物学工具，可以精确控制治疗细胞和遗传模块的功能，已经得到了快速的发展和应用，是一种强大的解决方案。经过精心设计和工程改造，它们可以用于微调治疗活动，即通过感应和处理用户定义的信号或生物标志物来调节剂量、生物活性有效载荷的产生。本文综述了用于重新编程治疗细胞的各种合成受体系统及其在生物医学研究中的广泛应用。特别关注了四个处于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，我们介绍了设计、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在治疗应用方面不断扩大的领域以及在临床转化方面当前面临的挑战。
