Recently, the research team led by Fei Wang and Chunhai Fan from Shanghai Jiao Tong University has developed a single-track DNA logic circuit using a temporally regulated DNA synchronizer. Compared to previously reported dual-track DNA circuits, this single-track architecture overcomes the fundamental limitation of unsupported multi-layer NOT operations, enabling the realization of arbitrary logical functions with a minimal number of DNA logic gates. The team has achieved the most compact 4-bit square root calculation circuit reported to date.

Article abstract:

DNA has emerged as a robust platform for engineering molecular circuits with arbitrary logic operations. Nevertheless, implementing DNA circuits for such functions generally relies on the use of dual-rail expression that doubles the number of required gates, constraining the achievable complexity in a single solution. A fundamental limitation is that conventional single-rail circuits cannot support nonfirst-layer NOT operations. Here, we introduce the design of a DNA synchronizer (DSN), a temporal regulation module that enables time-dependent NOT function, to circumvent the fundamental limitation of conventional single-rail designs. Tuning the binding affinity between the DSN strand and an inverter strand allows for regulating the execution time of NOT gates at varying cascade depths. Single-rail NAND and NOR gates are implemented using DSNs, which are Boolean complete. We further demonstrate a 4-bit square root circuit using a minimal set of only five gates. This single-rail architecture holds promise for developing compact yet scalable DNA computing circuits while advancing applications in diagnostics and therapeutics.