A Simple DNA Gate Motif for Synthesizing Large-Scale Circuits

(Extended Abstract)
  • Lulu Qian
  • Erik Winfree
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5347)


The prospects of programming molecular systems to perform complex autonomous tasks has motivated research into the design of synthetic biochemical circuits. Of particular interest to us are cell-free nucleic acid systems that exploit non-covalent hybridization and strand displacement reactions to create cascades that implement digital and analog circuits. To date, circuits involving at most tens of gates have been demonstrated experimentally. Here, we propose a DNA catalytic gate architecture that appears suitable for practical synthesis of large-scale circuits involving possibly thousands of gates.


Recognition Domain Threshold Gate Output Wire Gate Motif VHSIC Hardware Description Language 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tang, J., Breaker, R.R.: Rational design of allosteric ribozymes. Chem. Biol. 4, 453–459 (1997)CrossRefGoogle Scholar
  2. 2.
    Turberfield, A.J., Mitchell, J.C., Yurke, B., Mills Jr., A.P., Blakey, M.I., Simmel, F.C.: DNA fuel for free-running nanomachines. Physical Review Letters 90(11), 118102–118104 (2003)CrossRefGoogle Scholar
  3. 3.
    Zhang, D.Y., Turberfield, A.J., Yurke, B., Winfree, E.: Engineering entropy-driven reactions and networks catalyzed by DNA. Science 318, 1121–1125 (2007)CrossRefGoogle Scholar
  4. 4.
    Stojanovic, M.N., Mitchell, T.E., Stefanovic, D.: Deoxyribozyme-based logic gates. Journal of the American Chemical Society 124, 3555–3561 (2002)CrossRefGoogle Scholar
  5. 5.
    Hagiya, M., Yaegashi, S., Takahashi, K.: Computing with hairpins and secondary structures of DNA. In: Chen, J., Jonoska, N., Rozenberg, G. (eds.) Nanotechnology: Science and Computation, pp. 293–308. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  6. 6.
    Seelig, G., Soloveichik, D., Zhang, D.Y., Winfree, E.: Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006)CrossRefGoogle Scholar
  7. 7.
    Penchovsky, R., Breaker, R.R.: Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes. Nat. Biotechnol. 23(11), 1424–1433 (2005)CrossRefGoogle Scholar
  8. 8.
    Macdonald, J., Li, Y., Sutovic, M., Lederman, H., Pendri, K., Lu, W., Andrews, B.L., Stefanovic, D., Stojanovic, M.N.: Medium scale integration of molecular logic gates in an automaton. Nano Letters 6, 2598–2603 (2006)CrossRefGoogle Scholar
  9. 9.
    Yashin, R., Rudchenko, S., Stojanovic, M.N.: Networking particles over distance using oligonucleotide-based devices. Journal of the American Chemical Society 129, 15581–15583 (2007)CrossRefGoogle Scholar
  10. 10.
    Seeman, N.C.: An overview of structural DNA nanotechnology. Mol. Biotechnol. 37, 246–257 (2007)CrossRefGoogle Scholar
  11. 11.
    Bath, J., Turberfield, A.J.: DNA nanomachines. Nature Nanotechnology 2, 275–284 (2007)CrossRefGoogle Scholar
  12. 12.
    Gartner, Z.J., Liu, D.R.: The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules. Journal of the American Chemical Society 123, 6961–6963 (2001)CrossRefGoogle Scholar
  13. 13.
    Gothelf, K.V., LaBean, T.H.: DNA-programmed assembly of nanostructures. Organic & Biomolecular Chemistry 3, 4023–4037 (2005)CrossRefGoogle Scholar
  14. 14.
    Winfree, E., Liu, F., Wenzler, L.A., Seeman, N.C.: Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998)CrossRefGoogle Scholar
  15. 15.
    Rothemund, P.W.K.: Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006)CrossRefGoogle Scholar
  16. 16.
    Yin, P., Choi, H.M.T., Calvert, C.R., Pierce, N.A.: Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008)CrossRefGoogle Scholar
  17. 17.
    Turing, A.M.: The chemical basis of morphogenesis. Philosophical Transactions of the Royal Society (part B) 237, 37–72 (1953)MathSciNetCrossRefGoogle Scholar
  18. 18.
    Zhabotinsky, A.M.: A history of chemical oscillations and waves. Chaos 4, 379–386 (1991)CrossRefGoogle Scholar
  19. 19.
    Abelson, H., Allen, D., Coore, D., Hanson, C., Homsy, G., Knight Jr., T.F., Nagpal, R., Rauch, E., Sussman, G.J., Weiss, R.: Amorphous computing. Communications of the ACM 43, 74–82 (2000)CrossRefGoogle Scholar
  20. 20.
    Zhang, D.Y., Winfree, E.: Control of DNA strand displacement kinetics using toehold exchange (in preparation)Google Scholar
  21. 21.
    Yurke, B., Mills Jr., A.P.: Using DNA to power nanostructures. Genetic Programming and Evolvable Machines 4, 111–122 (2003)CrossRefGoogle Scholar
  22. 22.
    Dirks, R.M.: Analysis, design, and construction of nucleic acid devices. PhD thesis, California Institute of Technology (2005)Google Scholar
  23. 23.
    Bois, J.S.: Analysis of interacting nucleic acids in dilute solutions. PhD thesis, California Institute of Technology (2007)Google Scholar
  24. 24.
    Shannon, C.E.: A symbolic analysis of relay and switching circuits. Technical Report Master’s Thesis, Massachussetts Institute of Technology (1940)Google Scholar
  25. 25.
    Qian, L., Wang, Y., Zhang, Z., Zhao, J., Pan, D., Zhang, Y., Liu, Q., Fan, C., Hu, J., He, L.: Analogic china map constructed by DNA. Chinese Science Bulletin 51, 2973–2976 (2006)CrossRefGoogle Scholar
  26. 26.
    Douglas, S.M., Chou, J.J., Shih, W.M.: DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc. Nat. Acad. Sci. USA 104, 6644–6648 (2007)CrossRefGoogle Scholar
  27. 27.
    Thomas, D.E., Moorby, P.R.: The Verilog Hardware Description Language. Kluwer, Dordrecht (1991)CrossRefzbMATHGoogle Scholar
  28. 28.
    Golze, U.: VLSI Chip Design with the Hardware Description Language VERILOG. Springer, Heidelberg (1996)CrossRefGoogle Scholar
  29. 29.
    Shahdad, M., Lipsett, R., Marschner, E., Sheehan, K., Cohen, H., Waxman, R., Ackley, D.: VHSIC hardware description language. IEEE Computer 18, 94–103 (1985)CrossRefGoogle Scholar
  30. 30.
    Brenneman, A., Condon, A.: Strand design for biomolecular computation. Theor. Comput. Sci. 287, 39–58 (2002)MathSciNetCrossRefzbMATHGoogle Scholar
  31. 31.
    Bishop, M.A., D’Yachkov, A.G., Macula, A.J., Renz, T.E., Rykov, V.V.: Free energy gap and statistical thermodynamic fidelity of DNA codes. Journal of Computational Biology 14, 1088–1104 (2007)MathSciNetCrossRefGoogle Scholar
  32. 32.
    Mir, K.U.: A restricted genetic alphabet for DNA computing. In: Landweber, L.F., Baum, E.B. (eds.) DNA Based Computers II. DIMACS, vol. 44, pp. 243–246. American Mathematical Society, Providence (1998)Google Scholar
  33. 33.
    Braich, R.S., Chelyapov, N., Johnson, C., Rothemund, P.W.K., Adleman, L.M.: Solution of a 20-variable 3-SAT problem on a DNA computer. Science 296, 499–502 (2002)CrossRefGoogle Scholar
  34. 34.
    Faulhammer, D., Cukras, A.R., Lipton, R.J., Landweber, L.F.: Molecular computation: RNA solutions to chess problems. Proc. Nat. Acad. Sci. USA 97(3), 1385–1389 (2000)CrossRefGoogle Scholar
  35. 35.
    Panyutin, I.G., Hsieh, P.: Formation of a single base mismatch impedes spontaneous DNA branch migration. Journal of Molecular Biology 230, 413–424 (1993)CrossRefGoogle Scholar
  36. 36.
    Panyutin, I.G., Hsieh, P.: Kinetics of spontaneous DNA branch migration. Proc. Nat. Acad. Sci. USA 91, 2021–2025 (1994)CrossRefGoogle Scholar
  37. 37.
    Kao, M.-Y., Sanghi, M., Schweller, R.T.: Randomized fast design of short DNA words. In: Caires, L., Italiano, G.F., Monteiro, L., Palamidessi, C., Yung, M. (eds.) ICALP 2005. LNCS, vol. 3580, pp. 1275–1286. Springer, Heidelberg (2005)CrossRefGoogle Scholar
  38. 38.
    King, O.D.: Bounds for DNA codes with constant GC-content. Electronic Journal of Combinatorics 10, R33 (2003)MathSciNetzbMATHGoogle Scholar
  39. 39.
    Agilent Technologies. SurePrint technology (web page),
  40. 40.
    Agilent Technologies. Multi-pack gene expression microarrays (web page),
  41. 41.
    NimbleGen Systems, Inc. Array synthesis (web page),
  42. 42.
    Kohne, D.E., Levison, S.A., Byers, M.J.: Room temperature method for increasing the rate of DNA reassociation by many thousandfold: The phenol emulsion reassociation technique. Biochemistry 16, 5329–5341 (1977)CrossRefGoogle Scholar
  43. 43.
    Goldar, A., Sikorav, J.-L.: DNA renaturation at the water-phenol interface. Eur. Phys. J. E. 14, 211–239 (2004)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Lulu Qian
    • 1
  • Erik Winfree
    • 1
  1. 1.Computer Science, Computation & Neural Systems, and BioengineeringCalifornia Institute of TechnologyPasadenaUSA

Personalised recommendations