Synthetic DNA circuits for programming cell functions

Synthetic biology aims to re-engineer living cells into autonomous computational chassis capable of executing sophisticated biological tasks. Within this framework, programmable nucleic acid-based logic networks have emerged as a versatile molecular control layer for constructing intelligent cellular systems, offering unparalleled precision, orthogonality, and interoperability. Here, we highlight recent advances in molecular programming, focusing on the integration of synthetic DNA circuits within cellular environments to achieve logic-gated control of cellular functions. We first delineate the fundamental building blocks-including strand displacement, logic gates, amplifiers and neuromorphic architectures-and then examine strategies for interfacing these components with endogenous pathways. The field is currently witnessing a paradigm shift from ex vivo demonstration to in situ functional implementation, driven by the maturation of nucleic acid-based engineering within synthetic biology. Ultimately, these programmable molecular controllers enable the rational design of cellular behaviors, paving the way for next-generation precision therapeutics and autonomous biomanufacturing.