Multifunctional Clip Strand for the Regulation of DNA Strand Displacement and Construction of Complex DNA Nanodevices

Strand displacement reactions are important bricks for the construction of various DNA nanodevices, among which the toehold-mediated strand displacement reaction is the most prevalently adopted. However, only a limited number of tools could be used to finely regulate the toehold reaction, thus restricting DNA nanodevices from being more multifunctional and powerful. Herein, we developed a regulation tool, Clip, and achieved multiple regulatory functions, including subtle adjustment of the reaction rates, allosteric strand displacement, selective activation, and resetting of the reaction. Taking advantages of the multiple functions, we constructed Clip-toehold-based DNA walking machines. They showed behaviors of controllable walking, concatenation, and programmable pathways. Furthermore, we built Clip-toehold-based AND and OR logic gates and integrated those logic gates to construct multilayer circuits, which could be reset and reused to process different input signals. We believe that the proposed Clip tool has expanded the functionality of DNA strand displacement-based nanodevices to a much more complex and diverse level and anticipate that the tool will be widely adopted in DNA nanotechnology.