A nicking enzyme-assisted allosteric strategy for self-resetting DNA switching circuits

The self-regulation of biochemical reaction networks is crucial for maintaining balance, stability, and adaptability within biological systems. DNA switching circuits, serving as basic units, play essential roles in regulating pathways, facilitating signal transduction, and processing biochemical reaction networks. However, the non-reusability of DNA switching circuits hinders its application in current complex information processing. Herein, we proposed a nicking enzyme-assisted allosteric strategy for constructing self-resetting DNA switching circuits to realize complex information processing. This strategy utilizes the unique cleavage ability of the nicking enzyme to achieve the automatic restoration of states. Based on this strategy, we implemented a self-resetting DNA switch. By leveraging the reusability of the DNA switch, we constructed a DNA switching circuit with selective activation characteristics and further extended its functionality to include fan-out and fan-in processes by expanding the number of functional modules and connection modes. Furthermore, we demonstrated the complex information processing capabilities of these switching circuits by integrating recognition, translation, and decision functional modules, which could analyze and transmit multiple input signals and realize parallel logic operations. This strategy simplifies the design of switching circuits and promotes the future development of biosensing, molecular computing, and nanomachines.