Engineering Cells with Programmable Genetics and Fate by Frequency-encoded Light

To address this, we developed a frequency-modulated (FM) optogenetic platform that encodes temporal patterns of light stimulation into distinct transcriptional and functional outputs. Our synthetic gene circuits decode the frequency of light stimulation patterns into tunable gene expression with high fidelity and flexibility.

Using this framework, we achieve multiplexed control of multiple gene targets within single cells and supports programmable antigen presentation in tumor cells to guide CAR-T cell targeting in vitro and in vivo. Furthermore, our approach enables the dynamic regulation of cell-cell interactions and cell fate guidance, offering broad applications in synthetic biology, immunoengineering, and regenerative medicine. This work establishes a generalizable platform for remote, frequency-based programming of genetics and cell fate.