A Cationic Copolymer Enhances Responsiveness and Robustness of DNA Circuits

Abstract

AbstractToehold‐mediated DNA circuits are extensively employed to construct diverse DNA nanodevices and signal amplifiers. However, operations of these circuits are slow and highly susceptive to molecular noise such as the interference from bystander DNA strands. Herein, this work investigates the effects of a series of cationic copolymers on DNA catalytic hairpin assembly, a representative toehold‐mediated DNA circuit. One copolymer, poly(L‐lysine)‐graft‐dextran, significantly enhances the reaction rate by 30‐fold due to its electrostatic interaction with DNA. Moreover, the copolymer considerably alleviates the circuit's dependency on the length and GC content of toehold, thereby enhancing the robustness of circuit operation against molecular noise. The general effectiveness of poly(L‐lysine)‐graft‐dextran is demonstrated through kinetic characterization of a DNA AND logic circuit. Therefore, use of a cationic copolymer is a versatile and efficient approach to enhance the operation rate and robustness of toehold‐mediated DNA circuits, paving the way for more flexible design and broader application.