Implementing Molecular Logic Gates, Circuits, and Cascades Using DNAzymes

  • Matthew R. Lakin
  • Milan N. Stojanovic
  • Darko Stefanovic
Chapter
Part of the Emergence, Complexity and Computation book series (ECC, volume 23)

Abstract

The programmable nature of DNA chemistry makes it an attractive framework for the implementation of unconventional computing systems. Our early work in this area was among the first to use oligonucleotide-based logic gates to perform computations in a bulk solution. In this chapter we chart the development of this technology over the course of almost 15 years. We review our work on the implementation of DNA-based logic gates and circuits, which we have used to demonstrate digital logic circuits, autonomous game-playing automata, trainable systems and, more recently, decision-making circuits with potential diagnostic applications.

References

  1. 1.
    Adleman, L.M.: Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994)CrossRefGoogle Scholar
  2. 2.
    Aguirre, S.D., Ali, M.M., Kanda, P., Li, Y.: Detection of bacteria using fluorogenic DNAzymes. J. Vis. Exp. 63, e3961 (2012). doi:10.3791/3961
  3. 3.
    Aguirre, S.D., Ali, M.M., Salena, B.J., Li, Y.: A sensitive DNA enzyme-based fluorescent assay for bacterial detection. Biomolecules 3, 563–577 (2013). doi:10.3390/biom3030563 CrossRefGoogle Scholar
  4. 4.
    Ali, M.M., Aguirre, S.D., Lazim, H., Li, Y.: Fluorogenic DNAzyme probes as bacterial indicators. Angew. Chem. Int. Ed. 50, 3751–3754 (2011)CrossRefGoogle Scholar
  5. 5.
    Ali, M.M., Aguirre, S.D., Mok, W.W.K., Li, Y.: Developing fluorogenic RNA-cleaving DNAzymes for biosensing applications. In: Hartig, J.S., (ed.) Ribozymes, Methods in Molecular Biology, vol. 848, pp. 395–418. Springer, New York (2012)Google Scholar
  6. 6.
    Ali, M.M., Li, Y.: Colorimetric sensing using allosteric DNAzyme-coupled rolling circle amplification and a peptide nucleic acid-organic dye probe. Angew. Chem. Int. Ed. 48, 3512–3515 (2009)CrossRefGoogle Scholar
  7. 7.
    Alon, U.: An Introduction to Systems Biology: Design Principles of Biological Circuits. Chapman & Hall/CRC, Boca Raton (2007)Google Scholar
  8. 8.
    Bennett, C.H.: The thermodynamics of computation–a review. Int. J. Theor. Phys. 21(12), 905–940 (1982)CrossRefGoogle Scholar
  9. 9.
    Bhatt, S., Gething, P.W., Brady, O.J., Messina, J.P., Farlow, A.W., Moyes, C.L., Drake, J.M., Brownstein, J.S., Hoen, A.G., Sankoh, O., Myers, M.F., George, D.B., Jaenisch, T., Wint, G.R.W., Simmons, C.P., Scott, T.W., Farrar, J.J., Hay, S.I.: The global distribution and burden of dengue. Nature 496, 504–507 (2013). doi:10.1038/nature12060 CrossRefGoogle Scholar
  10. 10.
    Bone, S.M., Hasick, N.J., Lima, N.E., Erskine, S.M., Mokany, E., Todd, A.V.: DNA-only cascade: A universal tool for signal amplification, enhancing the detection of target analytes. Anal. Chem. 86(18), 9106–9113 (2014). doi:10.1021/ac501811r CrossRefGoogle Scholar
  11. 11.
    Brandsen, B.M., Velez, T.E., Sachdeva, A., Ibrahim, N.A., Silverman, S.K.: DNA-catalyzed lysine side chain modification. Angew. Chem. Int. Ed. 53(34), 9045–9050 (2014). doi:10.1002/anie.201404622 CrossRefGoogle Scholar
  12. 12.
    Breaker, R.R.: In vitro selection of catalytic polynucleotides. Chem. Rev. 97(2), 371–390 (1997)CrossRefGoogle Scholar
  13. 13.
    Breaker, R.R., Joyce, G.F.: A DNA enzyme with Mg\({}^{2+}\)-dependent RNA phosphoesterase activity. Chem. Biol. 2(10), 655–656 (1995)CrossRefGoogle Scholar
  14. 14.
    Brown III, C.W., Lakin, M.R., Fabry-Wood, A., Horwitz, E.K., Baker, N.A., Stefanovic, D., Graves, S.W.: A unified sensor architecture for isothermal detection of double-stranded DNA, oligonucleotides, and small molecules. ChemBioChem 16, 725–730 (2015). doi:10.1002/cbic.201402615 CrossRefGoogle Scholar
  15. 15.
    Brown III, C.W., Lakin, M.R., Horwitz, E.K., Fanning, M.L., West, H.E., Stefanovic, D., Graves, S.W.: Signal propagation in multi-layer DNAzyme cascades using structured chimeric substrates. Angew. Chem. Int. Ed. 53(28), 7183–7187 (2014). doi:10.1002/anie.201402691 CrossRefGoogle Scholar
  16. 16.
    Brown III, C.W., Lakin, M.R., Stefanovic, D., Graves, S.W.: Catalytic molecular logic devices by DNAzyme displacement. ChemBioChem 15, 950–954 (2014). doi:10.1002/cbic.201400047 CrossRefGoogle Scholar
  17. 17.
    Chandra, M., Sachdeva, A., Silverman, S.K.: DNA-catalyzed sequence-specific hydrolysis of DNA. Nat. Chem. Biol. 5(10), 718–720 (2009)CrossRefGoogle Scholar
  18. 18.
    Chandrasekar, J., Silverman, S.K.: Catalytic DNA with phosphatase activity. Proc. Natl. Acad. Sci. U.S. Am. 110(14), 5315–5320 (2013). doi:10.1073/pnas.1221946110 CrossRefGoogle Scholar
  19. 19.
    Chen, Y.J., Dalchau, N., Srinivas, N., Phillips, A., Cardelli, L., Soloveichik, D., Seelig, G.: Programmable chemical controllers made from DNA. Nat. Nanotechnol. 8, 755–762 (2013). doi:10.1038/nnano.2013.189 CrossRefGoogle Scholar
  20. 20.
    Credi, A.: Molecules that make decisions. Angew. Chem. Int. Ed. 46(29), 5472–5475 (2007)CrossRefGoogle Scholar
  21. 21.
    Dass, C.R.: Deoxyribozymes: cleaving a path to clinical trials. Trend. Pharmacol. Sci. 25(8), 395–397 (2004)CrossRefGoogle Scholar
  22. 22.
    Dass, C.R., Choong, P.F., Khachigian, L.M.: DNAzyme technology and cancer therapy: cleave and let die. Mol. Cancer Ther. 7(2), 243–251 (2008). doi:10.1158/1535-7163.MCT-07-0510 CrossRefGoogle Scholar
  23. 23.
    Dass, C.R., Galloway, S.J., Choong, P.F.: Dz13, a c-jun DNAzyme, is a potent inducer of caspase-2 activation. Oligonucleotides 20(3), 137–146 (2010). doi:10.1089/oli.2009.0226 CrossRefGoogle Scholar
  24. 24.
    Dass, C.R., Saravolac, E.G., Li, Y., Sun, L.Q.: Cellular uptake, distribution, and stability of 10–23 deoxyribozymes. Antisense Nucl. Acid Drug Dev. 12, 289–299 (2002)CrossRefGoogle Scholar
  25. 25.
    Dirks, R.M., Bois, J.S., Schaeffer, J.M., Winfree, E., Pierce, N.A.: Thermodynamic analysis of interacting nucleic acid strands. SIAM Rev. 49, 65–88 (2007)MathSciNetMATHCrossRefGoogle Scholar
  26. 26.
    Dirks, R.M., Pierce, N.A.: A partition function algorithm for nucleic acid secondary structure including pseudoknots. J. Comput. Chem. 24, 1664–1677 (2003)CrossRefGoogle Scholar
  27. 27.
    Dirks, R.M., Pierce, N.A.: An algorithm for computing nucleic acid base-pairing probabilities including pseudoknots. J. Comput. Chem. 25, 1295–1304 (2004)CrossRefGoogle Scholar
  28. 28.
    Eckhoff, G., Codrea, V., Ellington, A.D., Chen, X.: Beyond allostery: catalytic regulation of a deoxyribozyme through an entropy-driven DNA amplifier. J. Syst. Chem. 1, 13 (2010). doi:10.1186/1759-2208-1-13 CrossRefGoogle Scholar
  29. 29.
    Elahy, M., Dass, C.R.: Dz13: c-jun downregulation and tumour cell death. Chem. Biol. Drug Des. 78, 909–912 (2011). doi:10.1111/j.1747-0285.2011.01166.x CrossRefGoogle Scholar
  30. 30.
    Elbaz, J., Lioubashevski, O., Wang, F., Remacle, F., Levine, R.D., Willner, I.: DNA computing circuits using libraries of DNAzyme subunits. Nat. Nanotechnol. 5(6), 417–422 (2010)CrossRefGoogle Scholar
  31. 31.
    Elbaz, J., Moshe, M., Shlyahovsky, B., Willner, I.: Cooperative multicomponent self-assembly of nucleic acid structures for the activation of DNAzyme cascades: A paradigm for DNA sensors and aptasensors. Chemistry–A. Eur. J. 15, 3411–3418 (2009)CrossRefGoogle Scholar
  32. 32.
    Elbaz, J., Wang, F., Remacle, F., Willner, I.: PH-programmable DNA logic arrays powered by modular DNAzyme libraries. Nano Lett. 12, 6049–6054 (2012). doi:10.1021/nl300051g
  33. 33.
    Farfel, J., Stefanovic, D.: Towards practical biomolecular computers using microfluidic deoxyribozyme logic gate networks. In: Carbone, A., Pierce, N.A. (eds.) Proceedings of the 11th International Meeting on DNA Computing, Lecture Notes in Computer Science, vol. 3892, pp. 38–54. Springer, Heidelberg (2006)Google Scholar
  34. 34.
    Flynn-Charlebois, A., Wang, Y., Prior, T.K., Rashid, I., Hoadley, K.A., Coppins, R.L., Wolf, A.C., Silverman, S.K.: Deoxyribozymes with 2’-5’ RNA ligase activity. J. Am. Chem. Soc. 125, 2444–2454 (2003). doi:10.1021/ja028774y CrossRefGoogle Scholar
  35. 35.
    Gerasimova, Y.V., Cornett, E.M., Edwards, E., Su, X., Rohde, K.H., Kolpashchikov, D.M.: Deoxyribozyme cascade for visual detection of bacterial RNA. ChemBioChem 14, 2087–2090 (2013). doi:10.1002/cbic.201300471 CrossRefGoogle Scholar
  36. 36.
    Gerasimova, Y.V., Kolpashchikov, D.M.: Folding of 16S rRNA in a signal-producing structure for the detection of bacteria. Angew. Chem. Int. Ed. 52, 10586–10588 (2013). doi:10.1002/anie.201303919 CrossRefGoogle Scholar
  37. 37.
    Goldman, N., Bertone, P., Chen, S., Dessimoz, C., LeProust, E.M., Sipos, B., Birney, E.: Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494, 77–80 (2013). doi:10.1038/nature11875 CrossRefGoogle Scholar
  38. 38.
    Goudarzi, A., Lakin, M.R., Stefanovic, D.: DNA reservoir computing: a novel molecular computing approach. In: Soloveichik, D., Yurke, B. (eds.) Proceedings of the 19th International Conference on DNA Computing and Molecular Programming, Lecture Notes in Computer Science, vol. 8141, pp. 76–89. Springer, Heidelberg (2013). doi:10.1007/978-3-319-01928-4_6
  39. 39.
    Gu, H., Furukawa, K., Weinberg, Z., Berenson, D.F., Breaker, R.R.: Small, highly active DNAs that hydrolyze DNA. J. Am. Chem. Soc. 135, 9121–9129 (2013). doi:10.1021/ja403585e
  40. 40.
    He, S., Qu, L., Shen, Z., Tan, Y., Zeng, M., Liu, F., Jiang, Y., Li, Y.: Highly specific recognition of breast tumors by an RNA-cleaving fluorogenic DNAzyme probe. Anal. Chem. 87(1), 569–577 (2014). doi:10.1021/ac5031557 CrossRefGoogle Scholar
  41. 41.
    Huang, P.J.J., Liu, M., Liu, J.: Functional nucleic acids for detecting bacteria. Rev. Anal. Chem. 32(1), 77–89 (2013). doi:10.1515/revac-2012-0027 CrossRefGoogle Scholar
  42. 42.
    Huang, P.J.J., Vazin, M., Liu, J.: In vitro selection of a new lanthanide-dependent DNAzyme for ratiometric sensing lanthanides. Anal. Chem. 86(19), 9993–9999 (2014). doi:10.1021/ac5029962 CrossRefGoogle Scholar
  43. 43.
    Huang, P.J.J., Vazin, M., Matuszek, Z., Liu, J.: A new heavy lanthanide-dependent DNAzyme displaying strong metal cooperativity and unrescuable phosphorothioate effect. Nucleic Acid. Res. 43(1), 461–469 (2015). doi:10.1093/nar/gku1296 CrossRefGoogle Scholar
  44. 44.
    Hwang, K., Wu, P., Kim, T., Lei, L., Tian, S., Wang, Y., Lu, Y.: Photocaged DNAzymes as a general method for sensing metal ions in living cells. Angew. Chem. Int. Ed. 53, 13798–13802 (2014)CrossRefGoogle Scholar
  45. 45.
    Hayden, J.E., Riley, C.A., Burton, A.S., Lehman, N.: RNA-directed construction of structurally complex and active ligase ribozymes through recombination. RNA 11(11), 1678–1687 (2005). doi:10.1261/rna.2125305
  46. 46.
    Kahan-Hanum, M., Douek, Y., Adar, R., Shapiro, E.: A library of programmable DNAzymes that operate in a cellular environment. Sci. Rep. 3, 1535 (2013)CrossRefGoogle Scholar
  47. 47.
    Katz, E., Privman, V.: Enzyme-based logic systems for information processing. Chem. Soc. Rev. 39(5), 1835–1857 (2010)CrossRefGoogle Scholar
  48. 48.
    Kim, D.E., Joyce, G.F.: Cross-catalytic replication of an RNA ligase ribozyme. Chem. Biol. 11, 1505–1512 (2004). doi:10.1016/j.chembiol.2004.08.021 CrossRefGoogle Scholar
  49. 49.
    Kim, J., Winfree, E.: Synthetic in vitro transcriptional oscillators. Mol. Syst. Biol. 7, 465 (2011). doi:10.1038/msb.2010.119 CrossRefGoogle Scholar
  50. 50.
    Kim, S.H., Dass, C.R.: Induction of caspase-2 activation by a DNA enzyme evokes tumor cell apoptosis. DNA Cell Biol. 31(1) (2012). doi:10.1089/dna.2011.1323
  51. 51.
    Kolpashchikov, D.M.: A binary deoxyribozyme for nucleic acid analysis. ChemBioChem 8, 2039–2042 (2007)CrossRefGoogle Scholar
  52. 52.
    Kolpashchikov, D.M.: Binary probes for nucleic acid analysis. Chem. Rev. 110, 4709–4723 (2010)CrossRefGoogle Scholar
  53. 53.
    Kolpashchikov, D.M., Gerasimova, Y.V., Khan, M.S.: DNA nanotechnology for nucleic acid analysis: DX motif-based sensor. ChemBioChem 12, 2564–2567 (2011)CrossRefGoogle Scholar
  54. 54.
    Lake, A., Shang, S., Kolpashchikov, D.M.: Molecular logic gates connected through DNA four-way junctions. Angew. Chem. Int. Ed. 49, 4459–4462 (2010). doi:10.1002/anie.200907135 CrossRefGoogle Scholar
  55. 55.
    Lakin, M.R., Brown III, C.W., Horwitz, E.K., Fanning, M.L., West, H.E., Stefanovic, D., Graves, S.W.: Biophysically inspired rational design of structured chimeric substrates for DNAzyme cascade engineering. PLoS ONE 9(10), e110986 (2014). doi:10.1371/journal.pone.0110986
  56. 56.
    Lam, B.J., Joyce, G.F.: Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA. Nat. Biotechnol. 27(3), 288–292 (2009). doi:10.1038/nbt.1528 CrossRefGoogle Scholar
  57. 57.
    Lan, T., Furuya, K., Lu, Y.: A highly selective lead sensor based on a classic lead DNAzyme. Chem. Commun. 46, 3896–3898 (2010)CrossRefGoogle Scholar
  58. 58.
    Lederman, H., Macdonald, J., Stefanovic, D., Stojanovic, M.N.: Deoxyribozyme-based three-input logic gates and construction of a molecular full adder. Biochemistry 45(4), 1194–1199 (2006)CrossRefGoogle Scholar
  59. 59.
    Lee, C.S., Mui, T.P., Silverman, S.K.: Improved deoxyribozymes for synthesis of covalently branched DNA and RNA. Nucleic Acid. Res. 39(1), 269–279 (2011). doi:10.1093/nar/gkq753 CrossRefGoogle Scholar
  60. 60.
    Lee, J.H., Wang, Z., Liu, J., Lu, Y.: Highly sensitive and selective colorimetric sensors for uranyl (\({\rm {UO}}_{2}^{2+}\)): development and comparison of labeled and label-free DNAzyme-gold nanoparticle systems. J. Am. Chem. Soc. 130, 14217–14226 (2008)CrossRefGoogle Scholar
  61. 61.
    Levy, M., Ellington, A.D.: Exponential growth by cross-catalytic cleavage of deoxyribozymogens. Proc. Natl. Acad. Sci. U.S. Am. 100(11), 6416–6421 (2003). doi:10.1073/pnas.1130145100 CrossRefGoogle Scholar
  62. 62.
    Lincoln, T.A., Joyce, G.F.: Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009)CrossRefGoogle Scholar
  63. 63.
    Liu, J., Cao, Z., Lu, Y.: Functional nucleic acid sensors. Chem. Rev. 109, 1948–1998 (2009). doi:10.1021/cr030183i CrossRefGoogle Scholar
  64. 64.
    Lu, C.H., Wang, F., Willner, I.: Zn\(^{2+}\)-ligation DNAzyme-driven enzymatic and nonenzymatic cascades for the amplified detection of DNA. J. Am. Chem. Soc. 134(25), 10651–10658 (2012)CrossRefGoogle Scholar
  65. 65.
    Lund, K., Manzo, A.J., Dabby, N., Michelotti, N., Johnson-Buck, A., Nangreave, J., Taylor, S., Pei, R., Stojanovic, M.N., Walter, N.G., Winfree, E., Yan, H.: Molecular robots guided by prescriptive landscapes. Nature 465, 206–209 (2010)Google Scholar
  66. 66.
    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 Lett. 6(11), 2598–2603 (2006)CrossRefGoogle Scholar
  67. 67.
    Macdonald, J., Stefanovic, D., Stojanovic, M.N.: DNA computers for work and play. Sci. Am. 299(5), 84–91 (2008)CrossRefGoogle Scholar
  68. 68.
    McManus, S.A., Li, Y.: Turning a kinase deoxyribozyme into a sensor. J. Am. Chem. Soc. 135(19), 7181–7186 (2013)CrossRefGoogle Scholar
  69. 69.
    Mitchell, A., Dass, C.R., Sun, L.Q., Khachigian, L.M.: Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumour growth by DNAzymes targeting the zinc finger transcription factor EGR-1. Nucleic Acid. Res. 32(10), 3065–3069 (2004). doi:10.1093/nar/gkh626 CrossRefGoogle Scholar
  70. 70.
    Mokany, E., Bone, S.M., Young, P.E., Doan, T.B., Todd, A.V.: MNAzymes, a versatile new class of nucleic acid enzymes that can function as biosensors and molecular switches. J. Am. Chem. Soc. 132, 1051–1059 (2010). doi:10.1021/ja9076777 CrossRefGoogle Scholar
  71. 71.
    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). doi:10.1038/msb.2011.12 CrossRefGoogle Scholar
  72. 72.
    Mui, T.P., Silverman, S.K.: Convergent and general one-step DNA-catalyzed synthesis of multiply branched DNA. Organ. Lett. 10(20), 4417–4420 (2008)CrossRefGoogle Scholar
  73. 73.
    Muscat, R.A., Strauss, K., Ceze, L., Seelig, G.: DNA-based molecular architecture with spatially localized components. In: ISCA ’13: Proceedings of the 40th Annual International Symposium on Computer Architecture, pp. 177–188. ACM, New York (2013)Google Scholar
  74. 74.
    Olah, M.J., Stefanovic, D.: Superdiffusive transport by multivalent molecular walkers moving under load. Phys. Rev. E 87, 062713 (2013). doi:10.1103/PhysRevE.87.062713
  75. 75.
    Olea, Jr. C., Horning, D.P., Joyce, G.F.: Ligand-dependent exponential amplification of a self-replicating lRNA enzyme. J. Am. Chem. Soc. 134, 8050–8053 (2012). doi:10.1021/ja302197x
  76. 76.
    Orbach, R., Remacle, F., Levine, R.D., Willner, I.: DNAzyme-based 2:1 and 4:1 multiplexers and 1:2 demultiplexer. Chem. Sci. 5, 1074–1081 (2014)CrossRefGoogle Scholar
  77. 77.
    Osborne, S.E., Ellington, A.D.: Nucleic acid selection and the challenge of combinatorial chemistry. Chem. Rev. 97(2), 349–370 (1997)CrossRefGoogle Scholar
  78. 78.
    Parker, D.J., Xiao, Y., Aguilar, J.M., Silverman, S.K.: DNA catalysis of a normally disfavored RNA hydrolysis reaction. J. Am. Chem. Soc. 135(23), 8472–8475 (2013). doi:10.1021/ja4032488 CrossRefGoogle Scholar
  79. 79.
    Paul, N., Joyce, G.F.: A self-replicating ligase ribozyme. Proc. Natl. Acad. Sci. U.S. Am. 99(20), 12733–12740 (2002). doi:10.1073/pnas.202471099 CrossRefGoogle Scholar
  80. 80.
    Paul, N., Joyce, G.F.: Minimal self-replicating systems. Curr. Opin. Chem. Biol. 8, 634–639 (2004). doi:10.1016/j.cbpa.2004.09.005 CrossRefGoogle Scholar
  81. 81.
    Paul, N., Springsteen, G., Joyce, G.F.: Conversion of a ribozyme to a deoxyribozyme through in vitro evolution. Chem. Biol. 13, 329–338 (2006). doi:10.1016/j.chembiol.2006.01.007 CrossRefGoogle Scholar
  82. 82.
    Pei, R., Matamoros, E., Liu, M., Stefanovic, D., Stojanovic, M.N.: Training a molecular automaton to play a game. Nat. Nanotechnol. 5, 773–777 (2010)CrossRefGoogle Scholar
  83. 83.
    Pei, R., Taylor, S.K., Stefanovic, D., Rudchenko, S., Mitchell, T.E., Stojanovic, M.N.: Behavior of polycatalytic assemblies in a substrate-displaying matrix. J. Am. Chem. Soc. 128(39), 12693–12699 (2006)CrossRefGoogle Scholar
  84. 84.
    Peracchi, A.: Prospects for antiviral ribozymes and deoxyribozymes. Rev. Med. Virol. 14, 47–64 (2004). doi:10.1002/rmv.415
  85. 85.
    Plotnikov, A., Zehorai, E., Procaccia, S., Seger, R.: The MAPK cascades: Signaling components, nuclear roles and mechanisms of nuclear translocation. Biochimica et Biophysica Acta 1813, 1619–1633 (2011)CrossRefGoogle Scholar
  86. 86.
    Poje, J.E., Kastratovic, T., Macdonald, A.R., Guillermo, A.C., Troetti, S.E., Jabado, O.J., Fanning, M.L., Stefanovic, D., Macdonald, J.: Visual displays that directly interface and provide read-outs of molecular states via molecular graphics processing units. Angew. Chem. Int. Ed. 53(35), 9222–9225 (2014)CrossRefGoogle Scholar
  87. 87.
    Purtha, W.E., Coppins, R.L., Smalley, M.K., Silverman, S.K.: General deoxyribozyme-catalyzed synthesis of native 3’-5’ RNA linkages. J. Am. Chem. Soc. 127, 13124–13125 (2005). doi:10.1021/ja0533702 CrossRefGoogle Scholar
  88. 88.
    Qian, L., Soloveichik, D., Winfree, E.: Efficient Turing-universal computation with DNA polymers. In: Sakakibara, Y., Mi, Y. (eds.) Proceedings of the 16th International Conference on DNA Computing and Molecular Programming, Lecture Notes in Computer Science, vol. 6518, pp. 123–140. Springer, New York (2011)Google Scholar
  89. 89.
    Qian, L., Winfree, E.: Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011). doi:10.1126/science.1200520 CrossRefGoogle Scholar
  90. 90.
    Qian, L., Winfree, E.: Parallel and scalable computation and spatial dynamics with DNA-based chemical reaction networks on a surface. In: Murata, S., Kobayashi, S. (eds.) Proceedings of the 20th International Conference on DNA Computing and Molecular Programming, Lecture Notes in Computer Science, vol. 8727, pp. 114–131. Springer, New York (2014)Google Scholar
  91. 91.
    Qian, L., Winfree, E., Bruck, J.: Neural network computation with DNA strand displacement cascades. Nature 475, 368–372 (2011). doi:10.1038/nature10262 CrossRefGoogle Scholar
  92. 92.
    Robertson, M.P., Ellington, A.: In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nat. Biotechol. 17(1), 62–66 (1999)CrossRefGoogle Scholar
  93. 93.
    Santoro, S.W., Joyce, G.F.: A general purpose RNA-cleaving DNA enzyme. Proc. Natl. Acad. Sci. U.S. Am. 94, 4262–4266 (1997)CrossRefGoogle Scholar
  94. 94.
    Saunders, M.J., Edwards, B.S., Zhu, J., Sklar, L.A., Graves, S.W.: Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. In: Robinson, J.P. (ed.) Current Protocols in Cytometry Unit 13.12. Wiley, Hoboken (2010). doi:10.1002/0471142956.cy1312s54
  95. 95.
    Schaeffer, H.J., Weber, M.J.: Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol. Cell. Biol. 19(4), 2435–2444 (1999)CrossRefGoogle Scholar
  96. 96.
    Seelig, G., Soloveichik, D., Zhang, D.Y., Winfree, E.: Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006). doi:10.1126/science.1132493 CrossRefGoogle Scholar
  97. 97.
    Semenov, O., Olah, M.J., Stefanovic, D.: Cooperative linear cargo transport with molecular spiders. Nat. Comput. 12(2), 259–276 (2013). doi:10.1007/s11047-012-9357-2 MathSciNetCrossRefGoogle Scholar
  98. 98.
    Silverman, S.K.: Deoxyribozymes: DNA catalysts for bioorganic chemistry. Organ. Biomol. Chem. 2, 2701–2706 (2004)CrossRefGoogle Scholar
  99. 99.
    Silverman, S.K.: Catalytic DNA (deoxyribozymes) for synthetic applications—current abilities and future prospects. Chem. Commun. pp. 3467–3485 (2008). doi:10.1039/b807292m
  100. 100.
    Simmons, C.P., Farrar, J.J., van Vin Chau, N., Wills, B.: Dengue. New Engl. J. Med. 366, 1423–1432 (2012)Google Scholar
  101. 101.
    Soloveichik, D., Seelig, G., Winfree, E.: DNA as a universal substrate for chemical kinetics. Proc. Natl. Acad. Sci. U.S. Am. 107(12), 5393–5398 (2010). doi:10.1073/pnas.0909380107 CrossRefGoogle Scholar
  102. 102.
    Stefanovic, D., Stojanovic, M.N.: Computing game strategies. In: Computability in Europe: The Nature of Computation, pp. 383–392. Milano (2013)Google Scholar
  103. 103.
    Stojanovic, M.N., Mitchell, T.E., Stefanovic, D.: Deoxyribozyme-based logic gates. J. Am. Chem. Soc. 124, 3555–3561 (2002)CrossRefGoogle Scholar
  104. 104.
    Stojanovic, M.N., de Prada, P., Landry, D.W.: Catalytic molecular beacons. ChemBioChem 2, 411–415 (2001)CrossRefGoogle Scholar
  105. 105.
    Stojanovic, M.N., Semova, S., Kolpashchikov, D., Macdonald, J., Morgan, C., Stefanovic, D.: Deoxyribozyme-based ligase logic gates and their initial circuits. J. Am. Chem. Soc. 127, 6914–6915 (2005). doi:10.1021/ja043003a CrossRefGoogle Scholar
  106. 106.
    Stojanovic, M.N., Stefanovic, D.: Deoxyribozyme-based half adder. J. Am. Chem. Soc. 125(22), 6673–6676 (2003)CrossRefGoogle Scholar
  107. 107.
    Stojanovic, M.N., Stefanovic, D.: A deoxyribozyme-based molecular automaton. Nat. Biotechnol. 21(9), 1069–1074 (2003)CrossRefGoogle Scholar
  108. 108.
    Stojanovic, M.N., Stefanovic, D., Rudchenko, S.: Exercises in molecular computing. Acc. Chem. Res. 47, 1845–1852 (2014)CrossRefGoogle Scholar
  109. 109.
    Tabor, J.J., Levy, M., Ellington, A.D.: Deoxyribozymes that recode sequence information. Nucleic Acid. Res. 34, 2166–2172 (2006)CrossRefGoogle Scholar
  110. 110.
    Tang, J., Breaker, R.R.: Rational design of allosteric ribozymes. Chem. Biol. 4(6), 453–459 (1997)CrossRefGoogle Scholar
  111. 111.
    Teichmann, M., Kopperger, E., Simmel, F.C.: Robustness of localized DNA strand displacement cascades. ACS Nano 8(8), 8487–8496 (2014)CrossRefGoogle Scholar
  112. 112.
    Teller, C., Shimron, S., Willner, I.: Aptamer-DNAzyme hairpins for amplified biosensing. Anal. Chem. 81, 9114–9119 (2009)CrossRefGoogle Scholar
  113. 113.
    Tram, K., Kanda, P., Li, Y.: Lighting up RNA-cleaving DNAzymes for biosensing. J. Nucleic Acid. p. 958683 (2012). doi:10.1155/2012/958683
  114. 114.
    Tram, K., Kanda, P., Salena, B.J., Huan, S., Li, Y.: Translating bacterial detection by DNAzymes into a litmus test. Angew. Chem. Int. Ed. 53(47), 12799–12802 (2014). doi:10.1002/anie.201407021
  115. 115.
    Tyagi, S., Kramer, F.R.: Molecular beacons: probes that fluoresce upon hybridization. Nat. Biotechnol. 14(3), 303–309 (1996)CrossRefGoogle Scholar
  116. 116.
    Vaidya, N., Manapat, M.L., Chen, I.A., Xulvi-Brunet, R., Hayden, E.J., Lehman, N.: Spontaneous network formation among cooperative RNA replicators. Nature 491, 72–77 (2012). doi:10.1038/nature11549 CrossRefGoogle Scholar
  117. 117.
    Vaidya, N., Walker, S.I., Lehman, N.: Recycling of informational units leads to selection of replicators in a prebiotic soup. Chem. Biol. 20(2), 241–252 (2013). doi:10.1016/j.chembiol.2013.01.007 CrossRefGoogle Scholar
  118. 118.
    Wang, F., Elbaz, J., Orbach, R., Magen, N., Willner, I.: Amplified analysis of DNA by the autonomous assembly of polymers consisting of DNAzyme wires. J. Am. Chem. Soc. 133, 17149–17151 (2011)CrossRefGoogle Scholar
  119. 119.
    Wang, F., Elbaz, J., Teller, C., Willner, I.: Amplified detection of DNA through an autocatalytic and catabolic DNAzyme-mediated process. Angew. Chem. Int. Ed. 50, 295–299 (2011)CrossRefGoogle Scholar
  120. 120.
    Wang, F., Elbaz, J., Willner, I.: Enzyme-free amplified detection of DNA by an autonomous ligation DNAzyme machinery. J. Am. Chem. Soc. 134, 5504–5507 (2012)Google Scholar
  121. 121.
    Wang, F., Lu, C.H., Willner, I.: From cascaded catalytic nucleic acids to enzyme-DNA nanostructures: controlling reactivity, sensing, logic operations, and assembly of complex structures. Chem. Rev. 114, 2881–2941 (2014). doi:10.1021/cr400354z CrossRefGoogle Scholar
  122. 122.
    Wang, Y., Silverman, S.K.: Deoxyribozymes that synthesize branched and lariat RNA. J. Am. Chem. Soc. 125, 6880–6881 (2003). doi:10.1021/ja035150z CrossRefGoogle Scholar
  123. 123.
    Wang, Z., Lee, J.H., Lu, Y.: Label-free colorimetric detection of lead ions with a nanomolar detection limit and tunable dynamic range by using gold nanoparticles and DNAzyme. Adv. Mater. 20(17), 3263–3267 (2008)CrossRefGoogle Scholar
  124. 124.
    Wernick, W.: Complete sets of logical functions. Trans. Am. Math. Soc. 51, 117–132 (1942)MathSciNetMATHCrossRefGoogle Scholar
  125. 125.
    Wolfe, B.R., Pierce, N.A.: Sequence design for a test tube of interacting nucleic acid strands. ACS Synth. Biol. 4(10), 1086–1100 (2015). doi:10.1021/sb5002196
  126. 126.
    Wu, P., Hwang, K., Lan, T., Lu, Y.: A DNAzyme-gold nanoparticle probe for uranyl ion in living cells. J. Am. Chem. Soc. 135, 5254–5257 (2013). doi:10.1021/ja400150v CrossRefGoogle Scholar
  127. 127.
    Xiang, Y., Lu, Y.: Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets. Nat. Chem. 3, 697–703 (2011). doi:10.1038/nchem.1092 CrossRefGoogle Scholar
  128. 128.
    Xiang, Y., Lu, Y.: Expanding targets of DNAzyme-based sensors through deactivation and activation of DNAzymes by single uracil removal: Sensitive fluorescent assay of uracil-DNA glycosylase. Anal. Chem. 84, 9981–9987 (2012). doi:10.1021/ac302424f CrossRefGoogle Scholar
  129. 129.
    Xiang, Y., Wang, Z., Xing, H., Lu, Y.: Expanding DNAzyme functionality through enzyme cascades with applications in single nucleotide repair and tunable DNA-directed assembly of nanomaterials. Chem. Sci. 4, 398–404 (2013). doi:10.1039/c2sc20763j CrossRefGoogle Scholar
  130. 130.
    Xiang, Y., Wu, P., Tan, L.H., Lu, Y.: DNAzyme-functionalized gold nanoparticles for biosensing. In: Gu, M.B., Kim, H.S. (eds.) Biosensors Based on Aptamers and Enzymes, Advances in Biochemical Engineering/Biotechnology, vol. 140, pp. 93–120. Springer, New York (2014)Google Scholar
  131. 131.
    Xiao, Y., Wehrmann, R.J., Ibrahim, N.A., Silverman, S.K.: Establishing broad generality of DNA catalysts for site-specific hydrolysis of single-stranded DNA. Nucleic Acid. Res. 40(4), 1778–1786 (2012). doi:10.1093/nar/gkr860 CrossRefGoogle Scholar
  132. 132.
    Yashin, R., Rudchenko, S., Stojanovic, M.N.: Networking particles over distance using oligonucleotide-based devices. J. Am. Chem. Soc. 129(50), 15581–15584 (2007)CrossRefGoogle Scholar
  133. 133.
    Yurke, B., Mills Jr., A.P.: Using DNA to power nanostructures. Genet. Program. Evol. Mach. 4, 111–122 (2003). doi:10.1023/A:1023928811651 CrossRefGoogle Scholar
  134. 134.
    Yurke, B., Turberfield, A.J., Mills Jr., A.P., Simmel, F.C., Neumann, J.L.: A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000). doi:10.1038/35020524 CrossRefGoogle Scholar
  135. 135.
    Zadeh, J.N., Steenberg, C.D., Bois, J.S., Wolfe, B.R., Pierce, M.B., Khan, A.R., Dirks, R.M., Pierce, N.A.: NUPACK: analysis and design of nucleic acid systems. J. Comput. Chem. 32, 170–173 (2011)Google Scholar
  136. 136.
    Zadeh, J.N., Wolfe, B.R., Pierce, N.A.: Nucleic acid sequence design via efficient ensemble defect optimization. J. Comput. Chem. 32, 439–452 (2011)CrossRefGoogle Scholar
  137. 137.
    Zenisek, S.F.M., Hayden, E.J., Lehman, N.: Genetic exchange leading to self-assembling RNA species upon encapsulation in artificial protocells. Artif. Life 13(3), 279–289 (2007). doi:10.1162/artl.2007.13.3.279
  138. 138.
    Zhang, D.Y.: Cooperative hybridization of oligonucleotides. J. Am. Chem. Soc. 133, 1077–1086 (2011). doi:10.1021/ja109089q CrossRefGoogle Scholar
  139. 139.
    Zhang, D.Y., Seelig, G.: Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3, 103–113 (2011). doi:10.1038/nchem.957 CrossRefGoogle Scholar
  140. 140.
    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
  141. 141.
    Zhang, X.B., Kong, R.M., Lu, Y.: Metal ion sensors based on DNAzymes and related DNA molecules. Annu. Rev. Anal. Chem. 4, 105–128 (2011)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Matthew R. Lakin
    • 1
  • Milan N. Stojanovic
    • 2
  • Darko Stefanovic
    • 1
  1. 1.University of New MexicoAlbuquerqueUSA
  2. 2.Columbia UniversityNew YorkUSA

Personalised recommendations