pH‐Controlled DNA Switching Circuits with Multi‐State Responsiveness for Logic Computation and Control

Dynamic control of DNA circuit functionality is essential for constructing chemical reaction networks (CRNs) that implement complex functions. The triplex has been utilized for dynamically regulating the diverse functionalities of DNA circuits due to its distinctive pH responsiveness. However, it is challenging for triplexes to independently regulate the functionality of DNA circuits, as various triplexes were often required for DNA circuits to function in complex environments, which adds complexity to the design and control of dynamic circuits. Here, we proposed a pH-controlled multi-state DNA switching circuit construction strategy to realize dynamic regulation among three states through conformational transitions of the triplex. In addition, by leveraging the regulatory role of multi-state DNA switching circuits on the toehold-mediated strand displacement reaction, we constructed switchable DNA circuits for logic computation and control of hybridization chain reaction (HCR). We confirmed that the designed DNA switching circuits exhibited multi-state responsiveness, allowing for different logical operations at varying pH levels and programmable control of the diverse reaction pathways in the HCR. Our strategy offers a convenient approach for the intelligent response and dynamic regulation of large-scale CRNs and DNA nanostructure self-assembly. It promises applications in biosensing, disease detection and drug delivery.