Abstract

Synthetic Notch receptor is flourishing as a powerful tool for the accurate control of cell functions. It is a sensing receptor system developed based on the Notch signaling pathway. The synNotch receptors, combined with the downstream transcription programme, have the potential in constructing organoids and 3D tissues. It can also be used to track and visualize intercellular communication. Additionally, engineering synNotch cells carrying specific receptors significantly improve the efficacy and safety of immunotherapy. This review introduces the modular structure and multifaceted application direction of synNotch and summarizes four core design principles, which may become the key to the regulating receptor function. In addition, the advantages and limitations of synNotch receptors are summarized, providing new insights into the further use of synNotch receptors in biomedicine.