Enzyme-Free Nucleic Acid Logic Circuits

Abstract

Biological organisms perform complex information processing and control tasks using sophisticated biochemical circuits, yet the engineering of such circuits remains ineffective compared with that of electronic circuits. To systematically create complex yet reliable circuits, electrical engineers use digital logic, wherein gates and subcircuits are composed modularly and signal restoration prevents signal degradation. We report the design and experimental implementation of DNA-based digital logic circuits. We demonstrate AND, OR, and NOT gates, signal restoration, amplification, feedback, and cascading. Gate design and circuit construction is modular. The gates use single-stranded nucleic acids as inputs and outputs, and the mechanism relies exclusively on sequence recognition and strand displacement. Biological nucleic acids such as microRNAs can serve as inputs, suggesting applications in biotechnology and bioengineering.

Molecular implementation of simple logic programs

“…Such a cascading of computational steps is possible only when the inputs and outputs of each step are of the same type. Cascading of molecular computations has previously been shown by Seelig and colleagues 4 . Their system consists of DNA logic gates that require hours per logic gate operation, and the time per operation increases when operations are cascaded.…”

“…(Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision 2,4,8,9,11,12,19 . A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result.…”

“…Autonomous programmable computing devices made of biomolecules could interact with a biological environment and be used in future biological and medical applications [1][2][3][4][5][6][7] . Biomolecular implementations of finite automata 8,9 and logic gates 4,[10][11][12][13] have already been developed [14][15][16][17][18] .…”

“…Biomolecular implementations of finite automata 8,9 and logic gates 4,[10][11][12][13] have already been developed [14][15][16][17][18] . Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions.…”

The unnatural order of things

“…Base-pair interactions have, for example, been used to design basic logic circuits, including AND, OR and NOT gates 10 . Or, in a more disorderly approach to organization, DNA can aid the selfassembly of nanoparticles.…”