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Self-assembly of DNA into nanoscale three-dimensional shapes

An Erratum to this article was published on 25 June 2009


Molecular self-assembly offers a ‘bottom-up’ route to fabrication with subnanometre precision of complex structures from simple components1. DNA has proved to be a versatile building block2,3,4,5 for programmable construction of such objects, including two-dimensional crystals6, nanotubes7,8,9,10,11, and three-dimensional wireframe nanopolyhedra12,13,14,15,16,17. Templated self-assembly of DNA18 into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase ‘scaffold strand’ that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide ‘staple strands’19,20. Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes—monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross—with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.

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Figure 1: Design of three-dimensional DNA origami.
Figure 2: Three-dimensional DNA origami shapes.
Figure 3: Gel and TEM analysis of folding conditions for three-dimensional DNA origami.
Figure 4: Two-step hierarchical assembly of larger three-dimensional structures and polymers.


  1. Whitesides, G. M., Mathias, J. P. & Seto, C. T. Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science 254, 1312–1319 (1991)

    ADS  CAS  Article  Google Scholar 

  2. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982)

    CAS  PubMed  Google Scholar 

  3. Fu, T. J. & Seeman, N. C. DNA double-crossover molecules. Biochemistry 32, 3211–3220 (1993)

    CAS  Article  Google Scholar 

  4. Li, X. J., Yang, X. P., Qi, J. & Seeman, N. C. Antiparallel DNA double crossover molecules as components for nanoconstruction. J. Am. Chem. Soc. 118, 6131–6140 (1996)

    CAS  Article  Google Scholar 

  5. Seeman, N. C. DNA in a material world. Nature 421, 427–431 (2003)

    ADS  MathSciNet  Article  Google Scholar 

  6. Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998)

    ADS  CAS  Article  Google Scholar 

  7. Yan, H., Park, S. H., Finkelstein, H., Reif, J. H. & LaBean, T. H. DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301, 1882–1884 (2003)

    ADS  CAS  Article  Google Scholar 

  8. Rothemund, P. W. et al. Design and characterization of programmable DNA nanotubes. J. Am. Chem. Soc. 126, 16344–16352 (2004)

    CAS  Article  Google Scholar 

  9. Mathieu, F. et al. Six-helix bundles designed from DNA. Nano Lett. 5, 661–665 (2005)

    ADS  CAS  Article  Google Scholar 

  10. 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)

    ADS  CAS  Article  Google Scholar 

  11. Yin, P. et al. Programming DNA tube circumferences. Science 321, 824–826 (2008)

    ADS  CAS  Article  Google Scholar 

  12. Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005)

    ADS  CAS  Article  Google Scholar 

  13. Chen, J. H. & Seeman, N. C. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350, 631–633 (1991)

    ADS  CAS  Article  Google Scholar 

  14. Zhang, Y. & Seeman, N. C. The construction of a DNA truncated octahedron. J. Am. Chem. Soc. 116, 1661–1669 (1994)

    CAS  Article  Google Scholar 

  15. He, Y. et al. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452, 198–201 (2008)

    ADS  CAS  Article  Google Scholar 

  16. Zhang, C. et al. Conformational flexibility facilitates self-assembly of complex DNA nanostructures. Proc. Natl Acad. Sci. USA 105, 10665–10669 (2008)

    ADS  CAS  Article  Google Scholar 

  17. 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)

    ADS  CAS  Article  Google Scholar 

  18. Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002)

    ADS  CAS  Article  Google Scholar 

  19. Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006)

    ADS  CAS  Article  Google Scholar 

  20. Yan, H., LaBean, T. H., Feng, L. & Reif, J. H. Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proc. Natl Acad. Sci. USA 100, 8103–8108 (2003)

    ADS  CAS  Article  Google Scholar 

  21. Douglas, S. M. et al. Rapid prototyping of three-dimensional DNA-origami shapes with caDNAno. Nucleic Acids Res (in the press)

  22. Mandelkern, M., Elias, J. G., Eden, D. & Crothers, D. M. The dimensions of DNA in solution. J. Mol. Biol. 152, 153–161 (1981)

    CAS  Article  Google Scholar 

  23. Diekmann, S. & Lilley, D. M. J. The anomalous gel migration of a stable cruciform: temperature and salt dependence, and some comparisons with curved DNA. Nucleic Acids Res. 15, 5765–5774 (1987)

    CAS  Article  Google Scholar 

  24. Budker, V., Trubetskoy, V. & Wolff, J. A. Condensation of nonstoichiometric DNA/polycation complexes by divalent cations. Biopolymers 83, 646–657 (2006)

    CAS  Article  Google Scholar 

  25. Hibino, K. et al. Na+ more strongly inhibits DNA compaction by spermidin(3+) than K+. Chem. Phys. Lett. 426, 405–409 (2006)

    ADS  CAS  Article  Google Scholar 

  26. Garcia, H. G. et al. Biological consequences of tightly bent DNA: the other life of a macromolecular celebrity. Biopolymers 85, 115–130 (2007)

    CAS  Article  Google Scholar 

  27. Harris, J. R., Gerber, M., Gebauer, W., Wernicke, W. & Markl, J. Negative stains containing trehalose: application to tubular and filamentous structures. Microsc. Microanal. 2, 43–52 (1996)

    ADS  CAS  Article  Google Scholar 

  28. Douglas, S. M., Chou, J. J. & Shih, W. M. DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc. Natl Acad. Sci. USA 104, 6644–6648 (2007)

    ADS  CAS  Article  Google Scholar 

  29. Jungmann, R., Liedl, T., Sobey, T. L., Shih, W. & Simmel, F. C. Isothermal assembly of DNA origami structures using denaturing agents. J. Am. Chem. Soc. 130, 10062–10063 (2008)

    CAS  Article  Google Scholar 

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We thank X. Su for assistance in cloning M13-based scaffold sequences and G. Hess for pilot studies on the railed-bridge design. This work was supported by a Claudia Adams Barr Program Investigator grant, a Wyss Institute for Biologically Inspired Engineering at Harvard grant, and an NIH New Investigator grant (1DP2OD004641-01) to W.M.S., a Humboldt Fellowship to H.D., Deutscher Akademischer Austauschdienst (DAAD) Fellowship to T.L., and Swedish Science Council (Vetenskapsrådet) Fellowship to B.H.

Author Contributions S.M.D. designed the monolith and square nut, and provided caDNAno software support; H.D. designed the stacked cross; T.L. designed the railed bridge; B.H. designed the slotted cross; F.G. designed the genie bottle; W.M.S. designed the icosahedron; S.M.D. and W.M.S. developed the honeycomb-pleated-origami design rules; H.D., S.M.D., T.L., B.H. and W.M.S. optimized the folding and imaging conditions. All authors collected and analysed data and contributed to preparing the manuscript.

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Correspondence to William M. Shih.

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[Competing interests: W.M.S. is listed as inventor on a patent filed by Dan-Farber cancer institutes, entitled ‘Wireframe Nanostructures’ for the wireframe icosahedron described in Fig. 4, in April 2007.]

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Douglas, S., Dietz, H., Liedl, T. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).

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