We are learning to build synthetic molecular machinery from DNA. This research is inspired by biological systems in which individual molecules act, singly and in concert, as specialized machines: our ambition is to create new technologies to perform tasks that are currently beyond our reach. DNA nanomachines are made by self-assembly, using techniques that rely on the sequence-specific interactions that bind complementary oligonucleotides together in a double helix. They can be activated by interactions with specific signalling molecules or by changes in their environment. Devices that change state in response to an external trigger might be used for molecular sensing, intelligent drug delivery or programmable chemical synthesis. Biological molecular motors that carry cargoes within cells have inspired the construction of rudimentary DNA walkers that run along self-assembled tracks. It has even proved possible to create DNA motors that move autonomously, obtaining energy by catalysing the reaction of DNA or RNA fuels.
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Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).
Chen, J. H. & Seeman, N. C. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350, 631–633 (1991).
Zhang, Y. W. & Seeman, N. C. Construction of a DNA-truncated octahedron. J. Am. Chem. Soc. 116, 1661–1669 (1994).
Shih, W. M., Quispe, J. D. & Joyce, G. F. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004).
Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).
Robinson, B. H. & Seeman, N. C. The design of a biochip: a self-assembling molecular-scale memory device. Protein Eng. 1, 295–300 (1987).
Keren, K. et al. Sequence-specific molecular lithography on single DNA molecules. Science 297, 72–75 (2002).
Heilemann, M. et al. Multistep energy transfer in single molecular photonic wires. J. Am. Chem. Soc. 126, 6514–6515 (2004).
Niemeyer, C. M., Koehler, J. & Wuerdermann, C. DNA-directed assembly of bienzymic complexes from in vivo biotinylated NAD(P)H:FMN oxidoreductase and luciferase. ChemBioChem 3, 242–245 (2002).
Cate, J. H. et al. Crystal structure of a group I ribozyme domain: Principles of RNA packing. Science 273, 1678–1685 (1996).
DeGrado, W. F., Summa, C. M., Pavone, V., Nastri, F. & Lombardi, A. De novo design and structural characterization of proteins and metalloproteins. Annu. Rev. Biochem. 68, 779–819 (1999).
Chworos, A. et al. Building programmable jigsaw puzzles with RNA. Science 306, 2068–2072 (2004).
Pohl, F. M. & Joyin, T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J. Mol. Biol. 67, 375–396 (1972).
Mao, C., Sun, W., Shen, Z. & Seeman, N. C. A nanomechanical device based on the B-Z transition of DNA. Nature 397, 144–146 (1999).
Stryer, L. & Haugland, R. P. Energy transfer: a spectroscopic ruler. Proc. Natl Acad. Sci. USA 58, 719–726 (1967).
Yang, X., Vologodskii, A. V., Liu, B., Kemper, B. & Seeman, N. C. Torsional control of double-stranded DNA branch migration. Biopolymers 45, 69–83 (1998).
Holliday, R. A mechanism for gene conversion in fungi. Genet. Res. 5, 282–304 (1964).
Gehring, K., Leroy, J. L. & Gueron, M. A tetrameric DNA structure with protonated cytosine-cytosine base-pairs. Nature 363 561–565 (1993).
Aboul-ela, F., Murchie, A. I. H. & Lilley, D. M. J. NMR study of parallel-stranded tetraplex formation by the hexadeoxynucleotide d(TG4T). Nature 360, 280–282 (1992).
Liu, D. & Balasubramanian, S. A proton-fuelled DNA nanomachine. Angew. Chem. Int. Edn 42, 5734–5736 (2003).
Liu, D. et al. A reversible pH-driven DNA nanoswitch array. J. Am. Chem. Soc. 128, 2067–2071 (2006).
Liedl, T. & Simmel, F. C. Switching the conformation of a DNA molecule with a chemical oscillator. Nano Lett. 5, 1894–1898 (2005).
Liedl, T., Olapinksi, M. & Simmel, F. C. A surface-bound DNA switch driven by a chemical oscillator. Angew. Chem. Int. Edn 45, 5007–5010 (2006).
Shu, W. et al. DNA molecular motor driven micromechanical cantilever arrays. J. Am. Chem. Soc. 127, 17054–17060 (2005).
Baller, M. K. et al. A cantilever array-based artificial nose. Ultramicroscopy 82 1–9 (2001).
Chen, Y., Lee, S.-H. & Mao, C. A DNA nanomachine based on a duplex-triplex transition. Angew. Chem. Int. Edn 43, 5335–5338 (2004).
Brucale, M., Zuccheri, G. & Samori, B. The dynamic properties of an intramolecular transition from DNA duplex to cytosine-thymine motif triplex. Org. Biomol. Chem. 3, 575–577 (2005).
Yurke, B., Turberfield, A. J., Mills, A. P. Jr, Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).
Yurke, B. & Mills, A. P. Jr. Using DNA to power nanostructures. Genetic Programming and Evolvable Machines 4, 111–122 (2003).
Muller, B. K., Reuter, A., Simmel, F. C. & Lamb, D. C. Single-pair FRET characterization of DNA tweezers. Nano Lett. 6 2814–2820 (2006).
Simmel, F. C. & Yurke, B. Using DNA to construct and power a nanoactuator. Phys. Rev. E 63, 041913 (2001).
Simmel, F. C. & Yurke, B. A DNA-based molecular device switchable between three distinct mechanical states. Appl. Phys. Lett. 80, 883–885 (2002).
Yan, H., Zhang, X., Shen, Z. & Seeman, N. C. A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62–65 (2002).
Ding, B. & Seeman, N. C. Operation of a DNA robot arm inserted into a 2D DNA crystalline substrate. Science 314, 1583–1585.
Feng, L., Park, H., Reif, J. H. & Yan, H. A two-state DNA lattice switched by DNA nanoactuator. Angew. Chem. Int. Edn 42, 4342–4346 (2003).
Hazarika, P., Ceyhan, B. & Niemeyer, C. M. Reversible switching of DNA-gold nanoparticle aggregation. Angew. Chem. Int. Edn 43, 6469–6471 (2004).
Mirkin, C. A., Letsinger, R. L., Mucic, R. C. & Storhoff, J. J. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996).
Li, J. J. & Tan, W. A single DNA molecule nanomotor. Nano Lett. 2, 315–318 (2002).
Alberti, P. & Mergny, J.-L. DNA duplex-quadruplex exchange as the basis for a nanomolecular machine. Proc. Natl Acad. Sci. USA 100, 1569–1573 (2003).
Wang, Y. Zhang, Y. & Ong, N. P. Speeding up a single-molecule DNA device with a simple catalyst. Phys Rev. E 72, 051918 (2005).
Zhong, H. & Seeman, N. C. RNA used to control a rotary device. Nano Lett. 6, 2899–2903 (2006).
Dittmer, W. U. & Simmel, F. C. Transcriptional control of DNA-based nanomachines. Nano Lett. 4, 689–691 (2004).
Dittmer, W. U., Kempter, S., Radler, J. O. & Simmel, F. C. Using gene regulation to program DNA-based molecular devices. Small 7, 709–712 (2005).
Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).
Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000).
Becskei, A. & Serrano, L. Engineering stability in gene networks by autoregulation. Nature 405, 590–593 (2000).
Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006).
Erben, C. M., Goodman, R. P. & Turberfield, A. J. Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Edn 45, 7414–7417 (2006).
Svoboda, K., Schmidt, C. F., Schnapp, B. J. & Block, S. M. Direct observation of kinesin stepping byoptical trapping interferometry. Nature 365, 721–727 (1993).
Kuo, S. C. & Sheetz, M. P. Force of single kinesin groups measured with optical tweezers. Science 260, 232–234 (1993).
Finer, J. T., Simmons, R. M. & Spudich, J. A. Single myosin group mechanics: piconewton forces and nanometre steps. Nature 368, 113–119 (1994).
Ishijima, A. et al. Single-molecule analysis of the actomyosin motor using nano-manipulation. Biochem. Biophys. Res. Commun. 199, 1057–1063 (1994).
Shin, J.-S. & Pierce, N. A. Rewritable memory by controllable nanopatterning of DNA. Nano Lett. 4 905–909 (2004).
Shin, J.-S. & Pierce, N. A. A synthetic DNA walker for molecular transport. J. Am. Chem. Soc. 126, 10834–10835 (2004).
Tian, Y. & Mao, C. A pair of DNA circles continuously rolls against each other. J. Am. Chem. Soc. 126, 11410–11411 (2004).
Sherman, W. B. & Seeman, N. C. A precisely controlled DNA biped walking device. Nano Lett. 4, 1203–1207 (2004).
Mitchell, J. C., Harris, J. R., Malo, J., Bath, J. & Turberfield, A. J. Self-assembly of chiral DNA nanotubes. J. Am. Chem. Soc. 126, 16342–16343 (2004).
Rothemund, P. W. K. et al. Design and characterization of programmable DNA nanotubes. J. Am. Chem. Soc. 126, 16344–16352 (2004).
Liu, D., Park, S. H., Reif, J. H. & LaBean, T. H. DNA nanotubes self-assembled from triple-crossover tiles as templates for conductive nanowires. Proc. Natl Acad. Sci. USA 101, 717–722 (2004).
Mathieu, F. et al. Six-helix bundles designed from DNA. Nano Lett. 5, 661–665 (2005).
Lubrich, D., Bath, J. & Turberfield, A. J. Design and assembly of double-crossover linear arrays of micrometre length using rolling circle replication. Nanotechnology 16, 1574–1577 (2005).
Beyer, S., Nickels, P. & Simmel, F. C. Periodic DNA nanotemplates synthesized by rolling circle amplification. Nano Lett. 5, 719–722 (2005).
Deng, Z., Tian, Y., Lee, S. H., Ribbe, A. E. & Mao, C. DNA-encoded self-assembly of gold nanoparticles into one-dimensional arrays. Angew. Chem. Int. Edn 44, 3582–3585 (2005).
Rothermund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 298–302 (2006).
Higashi-Fujime, S. et al. The fastest actin-based motor protein from the green algae, Chara, and its distinct mode of interaction with actin. FEBS Lett. 375, 151–154 (1995).
Howard, J., Hudspeth, A. J. & Vale, R. D. Movement of microtubules by single kinesin molecules. Nature 342, 154–158 (1989).
Vale, R. D. & Milligan, R. A. The way things move: Looking under the hood of molecular motor proteins. Science 288, 88–95 (2000).
Santoro, S. W. & Joyce, G. F. A general purpose RNA-cleaving DNA enzyme. Proc. Natl Acad. Sci. USA 94, 4262–4266 (1997).
Chen, Y., Wang, M. & Mao, C. An autonomous DNA nanomotor powered by a DNA enzyme. Angew. Chem. Int. Edn 43, 3554–3557 (2004).
Tian, Y., He, Y., Peng, Y. & Mao, C. A DNA enzyme that walks processively and autonomously along a one-dimensional track. Angew. Chem. Int. Edn 44, 4355–4358 (2005).
Bath, J., Green, S. J. & Turberfield, A. J. A free-running DNA motor powered by a nicking enzyme. Angew. Chem. Int. Edn 44, 4358–4361 (2005).
Heiter, D. F., Lunnen, K. D. & Wilson, G. G. Site-specific DNA-nicking mutants of the heterodimeric restriction endonuclease R.BbvCI. J. Mol. Biol. 348, 631–640 (2005).
Bellamy, S. R. W. et al. Cleavage of individual DNA strands by the different subunits of the heterodimeric restriction endonuclease BbvCI. J. Mol. Biol. 348, 641–653 (2005).
Reif, J. H. The design of autonomous DNA nanomechanical devices: Walking and rolling DNA. Lect. Notes Comput. Sc. 2568, 22–37 (2003).
Yin, P., Turberfield, A. J., Sahu, S. & Reif, J. H. Designs for autonomous unidirectional walking DNA devices. Lect. Notes Comput. Sc. 3384, 410–425 (2005).
Yin, P., Yan, H., Daniell, X. G., Turberfield, A. J. & Reif, J. H. A unidirectional DNA walker that moves autonomously along a DNA track. Angew. Chem. Int. Edn 43, 4906–4911 (2004).
Benenson Y. et al. Programmable and autonomous computing machine made of biomolecules. Nature 414 430–434 (2001).
Yin, P., Sahu, S., Turberfield, A. J. & Reif, J. H. Design of autonomous DNA cellular automata. Lect. Notes Comput. Sc. 3892, 399–416 (2006).
Alberty, R. A. & Goldbert, R. N. Standard Thermodynamic Formation Properties for the Adenosine 5′-Triphosphate Series. Biochemistry 31, 10610–10615 (1992).
SantaLucia, J. A unified view of polymer, dumbell, and oligonucleotide nearest neighbour thermodynamics. Proc. Natl Acad. Sci. USA. 95, 1460–1465 (1998).
Turberfield, A. J. et al. DNA fuel for free-running nanomachines. Phys. Rev. Lett. 90, 118102 (2003).
Bois, J. S. et al. Topological constraints in nucleic acid hybridization kinetics. Nucleic Acids Res. 33, 4090–4095 (2005).
Dirks, R. M. & Pierce, N. A. (2004). Triggered amplification by hybridization chain reaction. Proc. Natl Acad. Sci. USA 101, 15275–1 5278.
Green, S. J., Lubrich, L. & Turberfield, A. J. DNA hairpins: fuel for autonomous DNA devices. Biophys. J. 91, 2966–2975 (2006).
Seelig, G., Yurke, B. & Winfree, E. DNA hybridization catalysts and catalyst circuits. Lect. Notes Comput. Sc. 3384, 329–343 (2005).
Seelig, G., Yurke, B. & Winfree, E. Catalysed relaxation of a metastable fuel. J. Am. Chem. Soc. 128, 12211–12220 (2006).
Kool, E. T. Replacing the nucleobases of DNA with designer molecules. Acc. Chem. Res. 35, 936–943 (2002).
Nielsen, P. E., Egholm M., Berg R. H. & Buchardt, O. Sequence-selective recognition of a DNA by strand displacement with a thymine-substituted polyamide. Science 254, 1497–1500 (1991).
Koshkin, A. A. et al. Synthesis of the adenin, cytosine, guanine, 5-methylcytosine, thimine and uracil bicyclonucleotide monomers, oligomerization, and unprecedented nucleic acid recognition. Tetrahedron 54, 3607–3630 (1998).
Smith, S. B., Finzi, L. & Bustamante, C. Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads. Science 258, 1122–1126 (1992).
Smith, S. B., Cui, Y. & Bustamante, C. Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science 271, 795–799 (1996).
Seeman, N. C. De novo design of sequences for nucleic-acid structural engineering. J. Biomol. Struc. Dyn. 8, 573–581 (1990).
Dirks, R. M., Lin, M., Winfree, E. & Pierce, N. A. Paradigms for computational nucleic acid design. Nucleic Acids Res. 32, 1392–1403 (2004).
Goodman, R. P. NANEV: a program employing evolutionary methods for the design of nucleic acid nanostructures. Biotechniques 38, 548–550 (2005).
Tashiro, R. & Sugiyama, H. A nanothermometer based on the different stackings of B- and Z-DNA. Angew. Chem. Int. Edn 42, 6018–6020 (2003).
Shen, W., Bruist, M. F., Goodman, S. D. & Seeman, N. C. A protein-driven DNA device that measures the excess binding energy of proteins that distort DNA. Angew. Chem. Int. Edn 43, 4750–4752 (2004).
Tyagi, S. & Kramer, F. R. Molecular beacons: probes that fluoresce upon hybridization. Nature Biotechnol. 14, 303–308 (1996).
Wilson, D.W. & Szostak, J. W. In vitro selection of functional nucleic acids. Ann. Rev. Biochem. 68, 611–648 (1999).
Dittmer, W. U., Reuter, A. & Simmel, F. C. A DNA-based machine that can cyclically bind and release thrombin. Angew. Chem. Int. Edn 43, 3550–3553 (2004).
Rusconi, C. P. et al. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419, 90–94 (2002).
Beyer, S. & Simmel, F. C. A modular DNA signal translator for the controlled release of a protein by an aptamer. Nucleic Acids Res. 34, 1581–1587 (2006).
Chelyapov, N. Allosteric aptamers controlling a signal amplification cascade allow visual detection of molecules at picomolar concentration. Biochemistry 45, 2461–2466 (2006).
Liu, J. & Lu, Y. A colorimetric lead biosensor using DNA enzyme-directed assembly of gold nanoparticles. J. Am. Chem. Soc. 125, 6642–6643 (2003).
Porta H. & Lizardi, P. M. An allosteric hammerhead ribozyme. Biotechnology 13, 161–164 (1995).
Stojanovic, M. N., de Prada, P. & Landry, D. W. Catalytic molecular beacons. ChemBioChem 2, 411–415 (2001).
Robertson, M. P. & Ellington, A. D. In vitro selection of an allosteric ribozyme that transduces analytes to amplicons. Nature Biotechnol. 17, 62–66 (1999).
Weizmann, Y. et al. A virus spotlighted by an autonomous DNA machine. Angew. Chem. Int. Edn 45, 7384–7388 (2006).
Van Ness, J., Van Ness, L. K. & Galas, D. J. Isothermal reactions for the amplification of oligonucleotides. Proc. Natl Acad. Sci USA 100, 4504–4509 (2003).
Stojanovic, M. N., Mitchell, T. E. & Stefanovic, D. Deoxyribozyme-based logic gates. J. Am. Chem. Soc. 124, 3555–3561 (2002).
Penchovsky, R. & Breaker, R. R. Computational design and experimental testing of oligonucleotide-sensing allosteric ribozyme. Nature Biotechnol. 23, 1424–1433 (2005).
Stojanovic, M. N. & Stefanovic, D. Deoxyribosome-based half adder. J. Am. Chem. Soc. 125 6673–6676 (2002).
Stojanovic, M. N. & Stefanovic, D. A deoxyribozyme-based molecular automaton. Nature Biotechnol. 21, 1069–1074 (2003).
Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).
Benenson, Y., Gil, B., Ben-Dor, U., Adar, R. & Shapiro, E. An autonomous molecular computer for logical control of gene expression. Nature 429, 423–428 (2004).
Isaacs, F. J. et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nature Biotechnol. 22, 841–847 (2005).
Bayer, T. S. & Smolke, C. D. Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nature Biotechnol. 23, 337–343 (2005).
Halpin, D. R. & Harbury, P. R. DNA display I: Sequence-encoded routing of DNA populations. PloS Biol. 2, 1015–1021 (2004).
Halpin, D. R. & Harbury, P. R. DNA display II: Genetic manipulation of combinatorial chemistry libraries for small-molecule evolution. PloS Biol. 2, 1022–1030 (2004).
Liao, S. & Seeman, N. C. Translation of DNA signals into polymer assembly instructions. Science 306, 2072–2074 (2004).
Gartner, Z. J. & Liu, D. R. The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules. J. Am. Chem. Soc. 123, 6961–6963 (2001).
Snyder, T. M. & Liu, D. R. Ordered multistep synthesis in a single solution directed by DNA templates. Angew. Chem. Int. Edn 44, 7379–7382 (2005).
Gothelf, K. V., Thomsen, A., Nielsen, M., Clo, E., & Brown, R. S. Modular DNA-programmed assembly of linear and branched conjugated nanostructures. J. Am. Chem. Soc. 126, 1044–1046 (2004).
Eckardt, L. H. et al. DNA nanotechnology: chemical copying of connectivity. Nature 420, 286 (2002).
Chen, Y. & Mao, C. Reprogramming DNA-directed reactions on the basis of a DNA conformational change. J. Am. Chem. Soc. 126, 13240–13241 (2004).
Chhabra, R., Sharma, J., Liu, Y. & Yan, H. Addressable molecular tweezers for DNA-templated coupling reactions. Nano Lett. 6, 978–983 (2006).
This work was supported by the UK research councils BBSRC, EPSRC and MRC, and by the MoD through the UK Bionanotechnology IRC.
The authors declare no competing financial interests.
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Bath, J., Turberfield, A. DNA nanomachines. Nature Nanotech 2, 275–284 (2007). https://doi.org/10.1038/nnano.2007.104
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