Abstract
DNA is a reliable biomolecule with which to build molecular computation systems. In particular, DNA logic circuits (diffusion-based) have shown good performance regarding scalability and correctness of computation. However, previous architectures of DNA logic circuits have two limitations. First, the speed of computation is slow, often requiring hours to compute a simple function. Second, the circuits are of high complexity regarding the number of DNA strands. Here, we introduce an architecture of DNA logic circuits based on single-stranded logic gates using strand-displacing DNA polymerase. The logic gates consist of only single DNA strands, which largely reduces leakage reactions and signal restoration steps such that the circuits are improved in regard to both speed of computation and the number of DNA strands needed. Large-scale logic circuits can be constructed from the gates by simple cascading strategies. In particular, we have demonstrated a fast and compact logic circuit that computes the square-root function of four-bit input numbers.
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The data used in this paper are available from the corresponding author upon proper request.
References
Watson, J. D. & Crick, F. H. Molecular structure of nucleic acids. Nature 171, 737–738 (1953).
Qian, L. & Winfree, E. Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011).
Qian, L., Winfree, E. & Bruck, J. Neural network computation with DNA strand displacement cascades. Nature 475, 368–372 (2011).
Chatterjee, G., Dalchau, N., Muscat, R. A., Phillips, A. & Seelig, G. A spatially localized architecture for fast and modular DNA computing. Nat. Nanotechnol. 12, 920 (2017).
Srinivas, N., Parkin, J., Seelig, G., Winfree, E. & Soloveichik, D. Enzyme-free nucleic acid dynamical systems. Science 358, eaal2052 (2017).
Cherry, K. M. & Qian, L. Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks. Nature 559, 370 (2018).
Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).
Thubagere, A. J. et al. Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 (2017).
Bui, H. et al. Localized DNA hybridization chain reactions on DNA origami. ACS Nano 12, 1146–1155 (2018).
Wang, B., Thachuk, C., Ellington, A. D., Winfree, E. & Soloveichik, D. Effective design principles for leakless strand displacement systems. Proc. Natl Acad. Sci. USA 115, E12182–E12191 (2018).
Thachuk, C., Winfree, E. & Soloveichik, D. in International Workshop on DNA-Based Computers Vol. 9211 (eds Phillips, A. & Yin, P.) 133–153 (Springer, 2015).
Boneh, D., Dunworth, C., Lipton, R. J. & Sgall, J. On the computational power of DNA. Discrete Appl. Math. 71, 79–94 (1996).
Ogihara, M. & Ray, A. Simulating boolean circuits on a DNA computer. Algorithmica 25, 239–250 (1999).
Winfree, E. Whiplash PCR for O(1) Computing (California Institute of Technology, 1998).
Baccouche, A., Montagne, K., Padirac, A., Fujii, T. & Rondelez, Y. Dynamic DNA-toolbox reaction circuits: a walkthrough. Methods 67, 234–249 (2014).
Montagne, K., Plasson, R., Sakai, Y., Fujii, T. & Rondelez, Y. Programming an in vitro DNA oscillator using a molecular networking strategy. Mol. Syst. Biol. 7, 466 (2011).
Padirac, A., Fujii, T. & Rondelez, Y. Bottom-up construction of in vitro switchable memories. Proc. Natl Acad. Sci. USA 109, E3212–E3220 (2012).
Aubert, N., Mosca, C., Fujii, T., Hagiya, M. & Rondelez, Y. Computer-assisted design for scaling up systems based on DNA reaction networks. J. R. Soc. Interface 11, 20131167 (2014).
van Roekel, H. W. et al. Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach. Chem. Soc. Rev. 44, 7465–7483 (2015).
Yordanov, B. et al. Computational design of nucleic acid feedback control circuits. ACS Synth. Biol. 3, 600–616 (2014).
Kishi, J. Y., Schaus, T. E., Gopalkrishnan, N., Xuan, F. & Yin, P. Programmable autonomous synthesis of single-stranded DNA. Nat. Chem. 10, 155 (2018).
Acknowledgements
This work is supported by NSF Grants nos. CCF-1320360, CCF-1217457, CCF-1617791 and CCF-1813805.
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T.S. and J.R. designed the logic gates and circuits. T.S. designed and performed the experiments. T.S. analysed the data. T.S. and J.R. wrote the paper. A.E., S.S., H.B., D.F., M.Y. and R.M. contributed to creating the logic gates and circuits. All authors discussed the design and results of the experiments. All authors commented on the manuscript.
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Supplementary Sections 1–5, Figs. 1–7, Tables 1–13 and Ref. 1.
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Song, T., Eshra, A., Shah, S. et al. Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase. Nat. Nanotechnol. 14, 1075–1081 (2019). https://doi.org/10.1038/s41565-019-0544-5
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DOI: https://doi.org/10.1038/s41565-019-0544-5
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