DNA-based biocomputing circuits and their biomedical applications

DNA-based biocomputing circuits are chemical reaction networks with information-processing capability that take advantage of DNA molecular interactions. The high parallelism and intrinsic biocompatibility of DNA circuits allows liquid-phase computing for various biomedical applications. In this Review, we examine the design rules and implementation strategies of DNA circuits, outlining the engineering and function of DNA computing units, including switches, logic gates, amplifiers and neurons. We further discuss the integration of these computing units into DNA circuits by 3D free diffusion, surface-confined diffusion, localized diffusion using DNA nanostructures, and algorithmic assembly. Furthermore, we investigate how the temporal dynamics of DNA circuits can be regulated and highlight their application in cellular imaging, biosensing and diagnostics, in conditional therapeutics, and for the rewiring of endogenous gene networks. Finally, we discuss the challenges that remain to be addressed for the clinical translation DNA-based biocomputing, outlining key future research directions. DNA computing takes advantage of DNA molecular interactions to achieve information processing for liquid-phase computing. This Review discusses designing rules, implementation strategies and biomedical applications of DNA computing circuits.