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Science 16 November 2007:
Vol. 318. no. 5853, pp. 1121 - 1125
DOI: 10.1126/science.1148532

Reports

Engineering Entropy-Driven Reactions and Networks Catalyzed by DNA

David Yu Zhang,1{dagger} Andrew J. Turberfield,2 Bernard Yurke,3* Erik Winfree1{dagger}

Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.

1 Computation and Neural Systems, California Institute of Technology, MC 136-93, 1200 East California Boulevard, Pasadena, CA91125, USA.
2 Department of Physics, University of Oxford, Clarendon Laboratory, Parks Road, Oxford OX1 3PU, UK.
3 Bell Laboratories, Alcatel-Lucent, Murray Hill, NJ 07974, USA.

* Present address: Materials Science and Engineering Department, Boise State University, Boise, ID 83725, USA.

{dagger} To whom correspondence should be addressed. E-mail: winfree{at}caltech.edu (E.W.); dzhang{at}dna.caltech.edu (D.Y.Z.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)