LAUSR

DNA-based Boolean logic gates (for example, AND, OR, and NOT) can be assembled into complex computational circuits that generate an output signal in response to specific patterns of oligonucleotide inputs. However, the fundamental nature of NOT gates, which convert the absence of an input into an output, makes their implementation within DNA-based circuits difficult. Premature execution of a NOT gate before completion of its upstream computation introduces an irreversible error into the circuit. By utilizing photocaging groups, we developed a novel DNA gate design that prevents gate function until irradiation at a certain time point. Optical activation provides temporal control over circuit performance by preventing premature computation and is orthogonal to all other components of DNA computation devices. Using this approach, we designed NAND and NOR logic gates that respond to synthetic microRNA sequences. We further demonstrate the utility of the NOT gate within multilayer circuits in response to a specific pattern of four microRNAs.