pH-Controlled Detachable DNA Circuitry and Its Application in Resettable Self-Assembly of Spherical Nucleic Acids.

Toehold-mediated strand displacement reaction, the fundamental basis in dynamic DNA nanotechnology, has proven its extraordinary power in programming dynamic molecular systems. Programmed activation of the toehold in a DNA substrate is crucial for building sophisticated DNA devices with digital and dynamic behaviors. Here we developed a detachable DNA circuit by embedding a pH-controlled intermolecular triplex between the toehold and branch migration domain of the traditional "linear substrate". The reaction rate and the "on/off" state of the detachable circuit can be regulated by varying the pHs. Similarly, a two-input circuit composed of three pH-responsive DNA modules was then constructed. Most importantly, a resettable self-assembly system of spherical nucleic acids was built by utilizing the high detachability of the intermolecular triplex structure-based DNA circuit. This work demonstrated a dynamic DNA device that can be repeatedly operated at constant temperature without generating additional waste DNA products. Moreover, this strategy showed an example of recycling waste spherical nucleic acids from a self-assembly system of spherical nucleic acids. Our strategy will provide a facile approach for dynamic regulation of complex molecular systems and reprogrammable nanoparticle assembly structures.