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Programmable chemical controllers made from DNA

Abstract

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

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Figure 1: DNA realization of a formal CRN.
Figure 2: DNA gate production.
Figure 3: Testing fundamental reaction types.
Figure 4: Tuning the rate of the bimolecular reaction A + B → C.
Figure 5: Consensus network.

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Acknowledgements

The authors thank E. Winfree, E. Klavins and D.Y. Zhang for discussions and comments on the manuscript. This work was supported by the National Science Foundation (grant NSF-CCF 1117143 to G.S. and D.S.). G.S. was supported by a Burroughs Wellcome Career Award at the Scientific Interface. D.S. was supported by an NIGMS Systems Biology Center grant (P50 GM081879).

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All authors designed the experiments and co-wrote the paper. Y-J.C. performed the wetlab experiments. N.D. and A.P. performed computational experiments.

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Correspondence to David Soloveichik or Georg Seelig.

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Chen, YJ., Dalchau, N., Srinivas, N. et al. Programmable chemical controllers made from DNA. Nature Nanotech 8, 755–762 (2013). https://doi.org/10.1038/nnano.2013.189

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