Progress in DNA Computing Based on Switch Circuits

[ Instrument Network Instrument R & D ] Recently, the Laboratory of Physical Biology, Center of Light Source Science, Shanghai Institutes of Advanced Research, Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, and Shanghai Jiaotong University have jointly developed a switch circuit based on DNA strand displacement reaction to realize digital Operation. Compared with commonly used logic gate circuits, the switch circuit has a simplified structure and can achieve a high signal-to-noise ratio and a fast-calculated molecular circuit with a minimum of DNA sequences. They showed a 4-bit square root operation. Related papers were published in Nature Communications under the title of Implementing digital computing with DNA-based switching circuits. Fei Wang and Lu Hui are co-first authors, and Fan Chunhai and Wang Lihua are co-corresponding authors.

DNA computing aims to use digital molecular reactions to achieve digital computing functions and is an important part of the field of biological computing. In particular, the DNA strand displacement reaction provides an important tool for constructing complex digital circuits that operate at room temperature. The DNA strand replacement reaction uses the difference in free energy of the hybridization of DNA molecules to replace one single strand from the double-helix structure of the hybrid DNA with one single-stranded sequence for subsequent reactions with precise sequence orthogonality. However, until now, DNA digital arithmetic circuits have been implemented based on logic gates, and the circuits are relatively complicated. As the number of DNA strands participating in the reaction increases, their operation speed and signal-to-noise ratio are limited. The switch circuit is a method proposed by Claude Elwood Shannon, the founder of information theory, in the early stages of the development of electronic circuits. It can efficiently and economically implement any digital function and is the basis of modern communication. Inspired by this, Fan Chunhai's team proposed a modular DNA molecular switch, which realized digital operation of any function experimentally by constructing a DNA switch circuit.

Similar to an electronic switch circuit, the DNA switch circuit controls the transmission of a current signal through a switching signal, and the direction of the current signal transmission can be precisely controlled by the difference in the free energy of the molecules in the reaction path. The upstream switch only has the S-domain response to the switching signal, while the downstream switch has the C-domain and the S-domain responding to the current signal of the previous stage and its own switching signal, respectively. Among them, the S domain implements function control, and the C domain implements current signal transmission. Using DNA molecular switches, they designed a full-function "switch drawing board", and any logic function can be realized by mapping the truth table to the current path on the "drawing board". The DNA switch circuit can experimentally realize a variety of circuit structures and functions including simple logic operations, fan-in and fan-out structures, complex combinational logic circuits, full adders, and 4-bit root operation. The calculation time of all circuits is within 10 minutes, showing complex DNA digital operations.

DNA switch circuit, as a new implementation method of DNA computing system, has laid the foundation for the development of molecular computers and the development of nano-machines with comprehensive decision-making capabilities or complex behavioral capabilities.