DNA Tetraplexes-Based Toehold Activation for Controllable DNA Strand Displacement Reactions

Most of the dynamic DNA devices are rationally constructed by utilizing toehold-mediated DNA strand displacement reactions. However, such approaches have been mainly limited to the operation with double-stranded hybridization and lack the versatility of DNA scaffold responses for additional levels of controlling DNA strand displacement reactions. Herein, we propose a toehold activation strategy based on the DNA tetraplex (G-quadruplex or i-motif), where the toehold domain is designed by attaching a complementary single-stranded segment (CS) to a G-rich/C-rich segment. Modulating G-quartet/C.C+ numbers and/or the CS lengths can easily tune the strand displacement kinetics. This scheme allows fine control of DNA strand displacement rates over 2 orders of magnitude by adjusting the concentration of various environmental stimuli. This strategy expands the rule set of designing dynamic DNA devices and will be useful in building diverse environmental stimuli-fuelled molecular devices.