Triplex-structure based DNA circuits with ultra-low leakage and high signal-to-noise ratio

DNA circuits are powerful tools in various applications such as logical computation, molecular diagnosis and synthetic biology. Leakage is a major problem in constructing complex DNA circuits. It directly affects the output signal and harms the circuit's performance significantly. In the traditional DNA circuits, the gate complex is a duplex structure. There are insufficient energy barriers to prevent spontaneous de-tachment of strands, resulting in a leak prone. Herein, we have developed triplex-structure based DNA circuit with ultra-low leakage and high signal-to-noise ratio (SNR). The triplex structure improves the stability in the absence of input. At the same time, the driving force of the strand displacement cascades reduces the influence of the triplex structure on the desired reaction. The SNR of the DNA circuit was increased to 695, while the desired reaction rate remained 90% of the conventional translator circuit. The triplex-structure mediated leakage prevention strategy was further tested at different temperatures and in DNA translator and seesaw circuits. We also constructed modular basic logic gates with a high efficiency and low leakage. On this basis, we further constructed triplex-structure based tertiary DNA logic circuits, and the SNR reached 295, which, to the best of our knowledge, was among the highest of the field. We believe that our scheme provides a novel, valid, and general tool for reducing leakages, and we anticipate that it will be widely adopted in DNA nanotechnology.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.