Enzyme-Free Nucleic Acid Logic Circuits

Georg Seelig,1 David Soloveichik,2 David Yu Zhang,2 Erik Winfree2,3*
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.

1 Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
2 Department of Computation and Neural Systems, California Institute of Technology, Pasadena, CA 91125, USA.
3 Department of Computer Science, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.

* To whom correspondence should be addressed. E-mail: winfree@caltech.edu