Cellular environment-responsive intelligent DNA logic circuits for controllable molecular sensing

Here we report smart molecular logic circuits built on a well-designed H-shaped DNA nanostructure that can recognize cell-simulated bioenvironments and modulate the operations of a DNA nanosensor. By assembling a wild-type ATP aptamer and a parallel G-quadruplex into the H-shaped DNA scaffold, two intrinsic cellular components, ATP and K+, are utilized to activate the logic circuits, enabling fluorescent detection of the target DNA via toehold-mediated strand displacement. In this way, two logic circuits consisting of cascaded “AND-AND” and “OR-AND” gates are achieved, which are responsive to the ATP and/or K+ concentration change outside and inside cells, and therefore control whether or not the downstream DNA sensor works. This work illustrates a novel concept for developing new bioinspired DNA molecular devices for not only programmable molecular sensing but also targeted drug delivery.