Skip to main content
SpringerLink
Log in

Implementing Molecular Logic Gates, Circuits, and Cascades Using DNAzymes

  • Chapter
  • First Online:
Advances in Unconventional Computing

Part of the book series: Emergence, Complexity and Computation ((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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adleman, L.M.: Molecular computation of solutions to combinatorial problems. Science 266, 1021–1024 (1994)

    Article  Google Scholar 

  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. 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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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)

    Article  Google Scholar 

  7. Alon, U.: An Introduction to Systems Biology: Design Principles of Biological Circuits. Chapman & Hall/CRC, Boca Raton (2007)

    Google Scholar 

  8. Bennett, C.H.: The thermodynamics of computation–a review. Int. J. Theor. Phys. 21(12), 905–940 (1982)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  12. Breaker, R.R.: In vitro selection of catalytic polynucleotides. Chem. Rev. 97(2), 371–390 (1997)

    Article  Google Scholar 

  13. Breaker, R.R., Joyce, G.F.: A DNA enzyme with Mg\({}^{2+}\)-dependent RNA phosphoesterase activity. Chem. Biol. 2(10), 655–656 (1995)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  17. Chandra, M., Sachdeva, A., Silverman, S.K.: DNA-catalyzed sequence-specific hydrolysis of DNA. Nat. Chem. Biol. 5(10), 718–720 (2009)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  20. Credi, A.: Molecules that make decisions. Angew. Chem. Int. Ed. 46(29), 5472–5475 (2007)

    Article  Google Scholar 

  21. Dass, C.R.: Deoxyribozymes: cleaving a path to clinical trials. Trend. Pharmacol. Sci. 25(8), 395–397 (2004)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  MathSciNet  MATH  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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. 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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. 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. 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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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)

    Article  Google Scholar 

  47. Katz, E., Privman, V.: Enzyme-based logic systems for information processing. Chem. Soc. Rev. 39(5), 1835–1857 (2010)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  49. Kim, J., Winfree, E.: Synthetic in vitro transcriptional oscillators. Mol. Syst. Biol. 7, 465 (2011). doi:10.1038/msb.2010.119

    Article  Google Scholar 

  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. Kolpashchikov, D.M.: A binary deoxyribozyme for nucleic acid analysis. ChemBioChem 8, 2039–2042 (2007)

    Article  Google Scholar 

  52. Kolpashchikov, D.M.: Binary probes for nucleic acid analysis. Chem. Rev. 110, 4709–4723 (2010)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. 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

    Article  Google Scholar 

  57. Lan, T., Furuya, K., Lu, Y.: A highly selective lead sensor based on a classic lead DNAzyme. Chem. Commun. 46, 3896–3898 (2010)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  62. Lincoln, T.A., Joyce, G.F.: Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009)

    Article  Google Scholar 

  63. Liu, J., Cao, Z., Lu, Y.: Functional nucleic acid sensors. Chem. Rev. 109, 1948–1998 (2009). doi:10.1021/cr030183i

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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)

    Article  Google Scholar 

  67. Macdonald, J., Stefanovic, D., Stojanovic, M.N.: DNA computers for work and play. Sci. Am. 299(5), 84–91 (2008)

    Article  Google Scholar 

  68. McManus, S.A., Li, Y.: Turning a kinase deoxyribozyme into a sensor. J. Am. Chem. Soc. 135(19), 7181–7186 (2013)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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. 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. 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)

    Article  Google Scholar 

  77. Osborne, S.E., Ellington, A.D.: Nucleic acid selection and the challenge of combinatorial chemistry. Chem. Rev. 97(2), 349–370 (1997)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  84. Peracchi, A.: Prospects for antiviral ribozymes and deoxyribozymes. Rev. Med. Virol. 14, 47–64 (2004). doi:10.1002/rmv.415

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. Qian, L., Winfree, E.: Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011). doi:10.1126/science.1200520

    Article  Google Scholar 

  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. Qian, L., Winfree, E., Bruck, J.: Neural network computation with DNA strand displacement cascades. Nature 475, 368–372 (2011). doi:10.1038/nature10262

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. Schaeffer, H.J., Weber, M.J.: Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol. Cell. Biol. 19(4), 2435–2444 (1999)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  MathSciNet  Google Scholar 

  98. Silverman, S.K.: Deoxyribozymes: DNA catalysts for bioorganic chemistry. Organ. Biomol. Chem. 2, 2701–2706 (2004)

    Article  Google Scholar 

  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. Simmons, C.P., Farrar, J.J., van Vin Chau, N., Wills, B.: Dengue. New Engl. J. Med. 366, 1423–1432 (2012)

    Google Scholar 

  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

    Article  Google Scholar 

  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. Stojanovic, M.N., Mitchell, T.E., Stefanovic, D.: Deoxyribozyme-based logic gates. J. Am. Chem. Soc. 124, 3555–3561 (2002)

    Article  Google Scholar 

  104. Stojanovic, M.N., de Prada, P., Landry, D.W.: Catalytic molecular beacons. ChemBioChem 2, 411–415 (2001)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  106. Stojanovic, M.N., Stefanovic, D.: Deoxyribozyme-based half adder. J. Am. Chem. Soc. 125(22), 6673–6676 (2003)

    Article  Google Scholar 

  107. Stojanovic, M.N., Stefanovic, D.: A deoxyribozyme-based molecular automaton. Nat. Biotechnol. 21(9), 1069–1074 (2003)

    Article  Google Scholar 

  108. Stojanovic, M.N., Stefanovic, D., Rudchenko, S.: Exercises in molecular computing. Acc. Chem. Res. 47, 1845–1852 (2014)

    Article  Google Scholar 

  109. Tabor, J.J., Levy, M., Ellington, A.D.: Deoxyribozymes that recode sequence information. Nucleic Acid. Res. 34, 2166–2172 (2006)

    Article  Google Scholar 

  110. Tang, J., Breaker, R.R.: Rational design of allosteric ribozymes. Chem. Biol. 4(6), 453–459 (1997)

    Article  Google Scholar 

  111. Teichmann, M., Kopperger, E., Simmel, F.C.: Robustness of localized DNA strand displacement cascades. ACS Nano 8(8), 8487–8496 (2014)

    Article  Google Scholar 

  112. Teller, C., Shimron, S., Willner, I.: Aptamer-DNAzyme hairpins for amplified biosensing. Anal. Chem. 81, 9114–9119 (2009)

    Article  Google Scholar 

  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. 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. Tyagi, S., Kramer, F.R.: Molecular beacons: probes that fluoresce upon hybridization. Nat. Biotechnol. 14(3), 303–309 (1996)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  124. Wernick, W.: Complete sets of logical functions. Trans. Am. Math. Soc. 51, 117–132 (1942)

    Article  MathSciNet  MATH  Google Scholar 

  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. 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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. 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

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. 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)

    Article  Google Scholar 

  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. Zhang, D.Y.: Cooperative hybridization of oligonucleotides. J. Am. Chem. Soc. 133, 1077–1086 (2011). doi:10.1021/ja109089q

    Article  Google Scholar 

  139. Zhang, D.Y., Seelig, G.: Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3, 103–113 (2011). doi:10.1038/nchem.957

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

Download references

Acknowledgments

We acknowledge our other experimental collaborators, in particular, Joanne Macdonald, Sergei Rudchenko, Steven Graves, and Carl Brown, III. This material is based upon work supported by the National Science Foundation under grants 1027877, 1028238, and 1318833. M.R.L. gratefully acknowledges support from the New Mexico Cancer Nanoscience and Microsystems Training Center.

Author information

Authors and Affiliations

  1. University of New Mexico, Albuquerque, NM, 87131, USA

    Matthew R. Lakin & Darko Stefanovic

  2. Columbia University, New York, NY, 10032, USA

    Milan N. Stojanovic

Authors
  1. Matthew R. Lakin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milan N. Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Darko Stefanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew R. Lakin .

Editor information

Editors and Affiliations

  1. Unconventional ComputingCentre, University of the Westof England Unconventional ComputingCentre, Bristol, United Kingdom

    Andrew Adamatzky

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lakin, M.R., Stojanovic, M.N., Stefanovic, D. (2017). Implementing Molecular Logic Gates, Circuits, and Cascades Using DNAzymes. In: Adamatzky, A. (eds) Advances in Unconventional Computing. Emergence, Complexity and Computation, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-319-33921-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-33921-4_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-33920-7

  • Online ISBN: 978-3-319-33921-4

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation