Dynamic Control of Aptamer–Ligand Activity Using Strand Displacement Reactions

Nucleic acid aptamers are an expandable toolkit of sensors and regulators. To employ aptamer regulators within nonequilibrium molecular networks, the aptamer–ligand interactions should be tunable over time, so that functions within a given system can be activated or suppressed on demand. This is accomplished through complementary sequences to aptamers, which achieve programmable aptamer–ligand dissociation by displacing the aptamer from the ligand. We demonstrate the effectiveness of our simple approach on light-up aptamers as well as on aptamers inhibiting viral RNA polymerases, dynamically controlling the functionality of the aptamer–ligand complex. Mathematical models allow us to obtain estimates for the aptamer displacement kinetics. Our results suggest that aptamers, paired with their complement, could be used to build dynamic nucleic acid networks with direct control over a variety of aptamer-controllable enzymes and their downstream pathways.