Abstract
Structural DNA Nanotechnology uses unusual DNA motifs to build target shapes and arrangements. These unusual motifs are generated by reciprocal exchange of DNA backbones, leading to branched systems with many strands and multiple helical domains. The motifs may be combined by sticky ended cohesion, involving hydrogen bonding or covalent interactions. Other forms of cohesion involve edge-sharing or paranemic interactions of double helices. A large number of individual species have been developed by this approach, including polyhedral catenanes, a variety of single-stranded knots, and Borromean rings. In addition to these static species, DNA-based nanomechanical devices have been produced that are ultimately targeted to lead to nanorobotics. Many of the key goals of structural DNA nanotechnology entail the use of periodic arrays. A variety of 2D DNA arrays have been produced with tunable features, such as patterns and cavities. DNA molecules have be used successfully in DNA-based computation as molecular representations of Wang tiles, whose self-assembly can be programmed to perform a calculation. About 4 years ago, on the fiftieth anniversary of the double helix, the area appeared to be at the cusp of a truly exciting explosion of applications; this was a correct assessment, and much progress has been made in the intervening period.
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References
Seeman, N. C. (2005). Structural DNA Nanotechnology: An overview. In Sandra J. Rosenthal, & David W. Wright (Eds.), Methods in molecular biology 303: Bionanotechnology protocols (pp. 143–166). Totowa, NJ: Humana Press.
Watson, J. D., & Crick, F. H. C. (1953). A structure for deoxyribose nucleic acid. Nature, 171, 737–738.
Seeman, N. C. (1982). Nucleic acid junctions and lattices. Journal of Theoretical Biology, 99, 237–247.
Robinson, B. H., & Seeman, N. C. (1987). The design of a biochip. Protein Engineering, 1, 295–300.
Winfree, E. (1996). On the computational power of DNA annealing and ligation. In E. J. Lipton, & E. B. Baum (Eds.), DNA Based Computing (pp. 199–219). Providence, Am. Math. Soc.
Seeman, N. C. (2000). In the nick of space: Generalized nucleic acid complementarity and the development of DNA nanotechnology. Synlett, 2000, 1536–1548.
Cohen, S. N., Chang, A. C.Y., Boyer, H. W., & Helling, R. B. (1973). Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences of the United States of America, 70, 3240–3244.
Qiu, H., Dewan, J. C., & Seeman, N. C. (1997). A DNA decamer with a sticky end: The crystal structure of d-CGACGATCGT. Journal of Molecular Biology, 267, 881–898.
Zhang, X., Yan, H., Shen, Z., & Seeman, N. C. (2002). Paranemic cohesion of topologically-closed DNA molecules. Journal of the American Chemical Society, 124, 12940–12941.
Shih, W. M., Quispe, J. D., & Joyce, G. F. (2004). A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature, 427, 618–621.
Shen, Z., Yan, H., Wang, T., & Seeman, N. C. (2004). Paranemic crossover DNA: A generalized Holliday structure with applications in nanotechnology. Journal of the American Chemical Society, 126, 1666–1674.
Yan, H., & Seeman, N. C. (2003). Edge-sharing motifs in DNA nanotechnology. Journal of Supramolecular Chemistry, 1, 229–237.
Kuzuya, A., Wang, R., Sha, R., & Seeman, N. C. (2007). Six-helix and eight-helix DNA nanotubes assembled from half-tubes. NanoLetters (in press).
Seeman, N. C. (2001). DNA nicks and nodes and nanotechnology. NanoLetters, 1, 22–26.
Holliday, R. (1964). A mechanism for gene conversion in fungi. Genetical Research, 5, 282–304.
Fu, T.-J., & Seeman, N. C. (1993). DNA double crossover structures. Biochemistry, 32, 3211–3220.
Schwacha, A., & Kleckner, N. (1995). Identification of double Holliday junctions as intermediates in meiotic recombination. Cell, 83, 783–791.
LaBean, T., Yan, H., Kopatsch, J., Liu, F., Winfree, E., Reif, J. H., & Seeman, N. C. (2000). The construction, analysis, ligation and self-assembly of DNA triple crossover complexes. Journal of the American Chemical Society, 122, 1848–1860.
Yan, H., Zhang, X., Shen, Z., & Seeman, N. C. (2002). A robust DNA mechanical device controlled by hybridization topology. Nature, 415, 62–65.
Li, X., Yang, X., Qi, J., & Seeman, N. C. (1996). Antiparallel DNA double crossover molecules as components for nanoconstruction. Journal of the American Chemical Society, 118, 6131–6140.
Mathieu, F., Liao, S., Mao, C., Kopatsch, J., Wang, T., & Seeman, N. C. (2005). Six-helix bundles designed from DNA. NanoLetters, 5, 661–665.
Liu, D., Wang, M., Deng, Z., Walulu, R., & Mao, C. (2004). Tensegrity: construction of rigid DNA triangles with flexible four-arm DNA junctions. Journal of the American Chemical Society, 126, 2324–2325.
Zheng, J., Constantinou, P. E., Micheel, C., Alivisatos, A. P., Kiehl, R. A., & Seeman, N. C. (2006). 2D nanoparticle arrays show the organizational power of robust DNA motifs. NanoLetters, 6, 1502–1504.
Constantinou, P. E., Wang, T., Kopatsch, J, Israel, L. B., Zhang, X., Ding, B., Sherman, W. B., Wang, X, Zheng, J., Sha, R., & Seeman, N. C. (2006). Double cohesion in structural DNA nanotechnology. Organic & Biomolecular Chemistry, 4, 3414–3419.
Goodman, R. P., Schaap, I. A.T., Tardin, C. F., Erben, C. M., Berry, R. M., Schmidt, C. F., & Turberfield, A. J. (2005). Rapid chiral assembly of rigid DNA building blocks form molecular fabrication. Science, 310, 1661–1664.
Caruthers, M. H. (1985). Gene synthesis machines: DNA chemistry and its uses. Science, 230, 281–285.
Zhang, Y., & Seeman, N. C. (1992) A solid-support methodology for the construction of geometrical objects from DNA. Journal of the American Chemical Society, 114, 2656–2663.
Chen, J., & Seeman, N. C. (1991). The synthesis from DNA of a molecule with the connectivity of a cube. Nature, 350, 631–633.
Zhang, Y., & Seeman, N. C. (1994). The construction of a DNA truncated octahedron. Journal of the American Chemical Society, 116, 1661–1669.
Qi, J., Li, X., Yang, X., & Seeman, N. C. (1996). The ligation of triangles built from bulged three-arm DNA branched junctions. Journal of the American Chemical Society, 118, 6121–6130.
Hagerman, P. J. (1988). Flexibility of DNA. Annual Review of Biophysics and Biophysical Chemistry, 17, 265–286.
Seeman, N. C., Rosenberg, J. M., & Rich, A. (1976). Sequence specific recognition of double helical nucleic acids by proteins. Proceedings of the National Academy of Sciences of the United States of America, 73, 804–808.
Zhu, L., Lukeman, P. S., Canary, J. W., & Seeman, N. C. (2003). Nylon/DNA: single-stranded DNA with a covalently stitched nylon lining. Journal of the American Chemical Society, 125, 10178–10179.
Freier, S. M., & Altmann, K.-H. (1997). The ups and down of nucleic acid duplex stability. Nucleic Acids Research, 25, 4229–4243.
Nielsen, P. E., Egholm, M., Berg, R. H., Buchardt, O. (1991). Sequence selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science, 254, 1497–1500.
Lukeman, P. S., Mittal, A., & Seeman, N. C. (2004). Two dimensional PNA/DNA arrays: Estimating the helicity of unusual nucleic acid polymers. Chemical Communications, 2004, 1694–1695.
Seeman, N., & Kallenbach, N. R. (1983). Design of immobile nucleic acid junctions. Biophysical Journal, 44, 201–209.
Seeman, N. C. (1990). De novo design of sequences for nucleic acid structure engineering. Journal of Biomolecular Structure & Dynamics, 8, 573–581.
Ma, R.-I., Kallenbach, N. R., Sheardy, R. D., Petrillo, M. L., & Seeman, N. C. (1986). Three arm nucleic acid junctions are flexible. Nucleic Acids Research, 14, 9745–9753.
Kallenbach, N. R., Ma R. -I., & Seeman, N. C. (1983). An immobile nucleic acid junction constructed from oligonucleotides. Nature, 305, 829–831.
Wang, Y., Mueller, J. E., Kemper, B., & Seeman, N. C. (1991). The assembly and characterization of 5-Arm and 6-Arm DNA junctions. Biochemistry, 30, 5667–5674.
Wang, X., & Seeman, N. C. (2007). The assembly and characterization of 8-arm and 12-arm DNA branched junctions. Journal of the American Chemical Society (in press).
Petrillo, M. L., Newton, C. J., Cunningham, R. P., Ma, R.-I., Kallenbach, N. R., & Seeman N. C. (1988). Ligation and flexibility of four-arm DNA junctions. Biopolymers, 27, 1337–1352.
Eis, P. S., & Millar D. P. (1993). Conformational distributions of a four-way DNA junction revealed by time-resolved fluorescence resonance energy transfer. Biochemistry, 32, 13852–13860.
Chen, J., & Seeman, N. C. (1991). The electrophoretic properties of a DNA cube and its sub-structure catenanes. Electrophoresis, 12, 607–611.
Seeman, N. C. (1992). The design of single-stranded nucleic acid knots. Molecular Engineering, 2, 297–307.
Du, S. M., Stollar, B. D., & Seeman, N. C. (1995). A synthetic DNA molecule in three knotted topologies. Journal of the American Chemical Society, 117, 1194–200.
Mao, C., Sun, W., & Seeman, N. C. (1997). Assembly of Borromean rings from DNA. Nature, 386, 137–138.
Chichak, K. S., Cantrill, S. J., Pease, A. R., Chiu, S. H., Cave, G. W. V., Atwood, J. L., & Stoddart, J. F. (2004). Molecular Borromean rings. Science, 304, 1308–1312.
Sa-Ardyen, P., Vologodskii, A. V., & Seeman, N. C. (2003). The flexibility of DNA double crossover molecules. Biophysical Journal, 84, 3829–3837.
Winfree, E., Liu, F., Wenzler, L. A., Seeman, N. C. (1998). Design and self-assembly of two-dimensional DNA crystals. Nature, 394, 539–544.
Liu, F., Sha, R., & Seeman, N. C. (1999). Modifying the surface features of two-dimensional DNA crystals. Journal of the American Chemical Society, 121, 917–922.
Mao, C., Sun, W., & Seeman, N. C. (1999). Designed two-dimensional DNA Holliday junction arrays visualized by atomic force microscopy. Journal of the American Chemical Society, 121, 5437–5443.
Sha, R., Liu, F., Millar, D. P., & Seeman, N. C. (2000). Atomic force microscopy of parallel DNA branched junction arrays. Chemical Biology, 7, 743–751.
Sha, R., Liu, F., & Seeman, N. C. (2002). Atomic force measurement of the interdomain angle in symmetric Holliday junctions. Biochemistry, 41, 5950–5955.
Ding, B., & Seeman, N. C. (2004) Pseudohexagonal 2D DNA crystals from double crossover cohesion. Journal of the American Chemical Society, 126, 10230–10231.
Xiao, S., Liu, F., Rosen, A., Hainfeld, J. F., Seeman, N. C., Musier-Forsyth, K. M., & Kiehl, R. A. (2002). Self-assembly of nanoparticle arrays by DNA scaffolding. Journal of Nanoparticle Research, 4, 313–317.
Le, J. D., Pinto, Y., Seeman, N. C., Musier-Forsyth, K., Taton T. A., & Kiehl, R. A. (2004). Self-assembly of nanoelectronic component arrays by in situ hybridization to 2D DNA scaffolding. NanoLetters, 4, 2343–2347.
Pinto, Y. Y., Le, J. D., Seeman, N. C., Musier-Forsyth, K., Taton, T. A., & Kiehl, R. A. (2005). Sequence-encoded self-assembly of multiple-nanocomponent arrays by 2D DNA scaffolding. NanoLetters, 5, 2399–2402.
Garibotti, A. V., Knudsen, S. M., Ellington, A. D., & Seeman, N. C. (2006). Functional DNAzymes organized into 2D arrays. NanoLetters, 6, 1505–1507.
Chhabra, R., Sharma, J., Liu, Y., & Yan, H. (2006). Addressable molecular tweezers for DNA-templated coupling reactions. NanoLetters, 6, 978–983.
Ding, B., & Seeman, N. C. (2006). Operation of a DNA robot arm inserted into a 2D DNA crystalline substrate. Science, 314, 1583–1585.
Yang, X., Vologodskii, A. V., Liu, B., Kemper, B., & Seeman, N. C. (1998). Torsional control of double stranded DNA branch migration. Biopolymers, 45, 69–83.
Rich, A., Nordheim, A., Wang, A. H.-J. (1984). The chemistry and biology of left-handed Z-DNA. Annual Review of Biochemistry, 53, 791–846.
Mao, C., Sun, W., Shen, Z., & Seeman, N. C. (1999). A DNA nanomechanical device based on the B-Z transition. Nature, 397, 144–146.
Yurke, B., Turberfield, A. J., Mills, A. P., Jr., Simmel, F. C., & Neumann, J. L. (2000). A DNA-fuelled molecular machine made of DNA. Nature, 406, 605–608.
Sherman, W. B., & Seeman, N. C. (2004). A precisely controlled DNA bipedal walking device. NanoLetters, 4, 1203–1207.
Shin, J.-S., & Pierce, N. A. (2004). A synthetic DNA walker for molecular transport. Journal of the American Chemical Society, 126, 10834–10835.
Tian, Y., He, Y., Chen, Y., Yin, P., & Mao, C. (2005). Molecular devices—A DNAzyme that walks processively and autonomously along a one-dimensional track. Angewandte Chemie (International ed. in English), 44, 4355–4358.
Dittmer, W. U., & Simmel, F. C. (2004). Transcriptional control of DNA-based nanomachines. NanoLetters, 4, 689–691.
Seeman, N. C. (2005). From genes to machines: DNA nanomechanical devices. Trends in Biochemical Sciences, 30, 119–125.
Bath, J., & Turberfield, A. J. (2007). DNA nanomachines. Nature Nanotechnology, 2, 276–284.
Feng, L., Park, S. H., Reif, J. H., & Yan, H. (2003). A two-state DNA lattice switched by DNA nanoactuator. Angewandte Chemie (International ed. in English), 42, 4342–4346.
Liao, S., & Seeman, N. C. (2004). Translation of DNA signals into polymer assembly instructions. Science, 306, 2072–2074.
Adleman, L. (1994). Molecular computation of solutions to combinatorial problems. Science, 266, 1021–1024.
Grünbaum, B., & Shephard, G. C. (1986) Tilings & patterns. New York: Freeman.
Mao, C., LaBean, T., Reif, J. H., & Seeman, N. C. (2000). Logical computation using algorithmic self-assembly of DNA triple crossover molecules. Nature, 407, 493–496.
Rothemund, P. W. K., Papadakis, N., & Winfree, E. (2004). Algorithmic self-assembly of DNA Sierpinski triangles. PLOS Biology 2, 2041–2053.
Barish, R. D., Rothemund, P. W. K., & Winfree, E. (2005). Two computational primitives for algorithmic assembly: Copying and counting. NanoLetters, 5, 2586–2592.
Winfree, E. (2000). Algorithmic self-assembly of DNA: Theoretical motivations and 2D assembly experiments. Journal of Biomolecular Structure & Dynamics Conversat. 11(2), 263–270.
Lin, C. X., Katilius, E., Liu, Y., Zhang, J. P., & Yan, H. (2006). Self-assembled signaling aptamer DNA arrays for protein detection. Angewandte Chemie (International ed. in English), 45, 5296–5301.
Seeman N. C. (1991). The construction of 3-D stick figures from branched DNA. DNA and Cell Biology, 10, 475–486.
Eckardt, H. E., Naumann, K., Pankau, W. M., Rein, M., Schweitzer, M., Windhab, N., & von Kiedrowski, G. (2002). Chemical copying of connectivity. Nature, 420, 286.
Rothemund, P. W.K. (2006). Folding DNA to create nanoscale shapes and patterns. Nature, 440, 297–302.
Yan, H., LaBean, T. H., Feng, L., & Reif, J. H. (2003). Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proceedings of the National Academy of Sciences, 100, 8103–8108.
Douglas, S. M., Chou, J. J., & Shih, W. M. (2007). DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proceedings of the National Academy of Sciences of the United States of America, 104, 6644–6648.
Mao, C. Constantinou, P. E., Liu, F., Pinto, Y., Kopatsch, J, Lukeman, P. S., Wang, T., Ding, B., Yan, H., Birktoft, J. J., Sha, R., Zhong, H., Foley, L., Wenzler, L. A., Sweet, R., Becker, M. & Seeman, N. C. (2005). The design of self-assembled 3D DNA networks. In M. Cahay, M. Urquidi-Macdonald, S. Bandyopadhyay, P. Guo, H. Hasegawa, N. Koshida, J. P. Leburton, D. J., Lockwood, S. Seal, & A. Stella (Eds.), Proceedings of the International Symposium on the Nanoscale Devices, Materials, and Biological Systems, 206th Meeting of the Electrochemical Society, PV 2004-XX (Vol. 13, pp. 509–520). Honolulu.
Acknowledgments
I am grateful to all of my students, postdocs and collaborators for their contributions to the founding of structural DNA nanotechnology. This research has been supported by grants GM-29554 from NIGMS, grants DMI-0210844, EIA-0086015, CCF-0432009, CCF-0523290 and CTS-0548774, CTS-0608889 from the NSF, 48681-EL from ARO, DE-FG02-06ER64281 from DOE (Subcontract from the Research Foundation of SUNY), and a grant from the W.M. Keck Foundation.
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Seeman, N.C. An Overview of Structural DNA Nanotechnology. Mol Biotechnol 37, 246–257 (2007). https://doi.org/10.1007/s12033-007-0059-4
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DOI: https://doi.org/10.1007/s12033-007-0059-4