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A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron


Molecular self-assembly offers a means of spontaneously forming complex and well-defined structures from simple components. The specific bonding between DNA base pairs has been used in this way to create DNA-based nanostructures and to direct the assembly of material on the subnanometre to micrometre scale1,2. In principle, large-scale clonal production of suitable DNA sequences and the directed evolution of sequence lineages towards optimized behaviour3 can be realized through exponential DNA amplification by polymerases. But known examples of three-dimensional geometric DNA objects4,5,6 are not amenable to cloning because they contain topologies that prevent copying by polymerases1,2,7. Here we report the design and synthesis of a 1,669-nucleotide, single-stranded DNA molecule that is readily amplified by polymerases and that, in the presence of five 40-mer synthetic oligodeoxynucleotides, folds into an octahedron structure by a simple denaturation–renaturation procedure. We use cryo-electron microscopy to show that the DNA strands fold successfully, with 12 struts or edges joined at six four-way junctions to form hollow octahedra approximately 22 nanometres in diameter. Because the base-pair sequence of individual struts is not repeated in a given octahedron8,9, each strut is uniquely addressable by the appropriate sequence-specific DNA binder.

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Figure 1: Design of the DNA octahedron.
Figure 2: Gel-shift analysis of folding of the DNA octahedron.
Figure 3: Visualization of the DNA octahedron structure by cryo-electron microscopy.

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

    Article  MathSciNet  ADS  Google Scholar 

  2. Seeman, N. C. DNA nanotechnology: novel DNA constructions. Annu. Rev. Biophys. Biomol. Struct. 27, 225–248 (1998)

    Article  CAS  Google Scholar 

  3. Wilson, D. S. & Szostak, J. W. In vitro selection of functional nucleic acids. Annu. Rev. Biochem. 68, 611–647 (1999)

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Dorenbeck, A. . DNA Nanostructures by Self-Assembly of Trisoligonucleotidyls. Thesis, Univ. Bochum (2000)

    Google Scholar 

  7. Seeman, N. C. Construction of three-dimensional stick figures from branched DNA. DNA Cell Biol. 10, 475–486 (1991)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Seeman, N. C. De novo design of sequences for nucleic acid structural engineering. J. Biomol. Struct. Dyn. 8, 573–581 (1990)

    Article  CAS  Google Scholar 

  10. 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)

    Article  CAS  Google Scholar 

  11. Larson, S. B. et al. Double-helical RNA in satellite tobacco mosaic virus. Nature 361, 179–182 (1993)

    Article  CAS  ADS  Google Scholar 

  12. Tang, L. et al. The structure of Pariocoto virus reveals a dodecahedral cage of duplex DNA. Nature Struct. Biol. 8, 77–83 (2001)

    Article  CAS  Google Scholar 

  13. Zhang, X., Yan, H., Shen, Z. & Seeman, N. C. Paranemic cohesion of topologically-closed DNA molecules. J. Am. Chem. Soc. 124, 12940–12941 (2002)

    Article  CAS  Google Scholar 

  14. Sa-Ardyen, P., Vologodskii, A. V. & Seeman, N. C. The flexibility of DNA double crossover molecules. Biophys. J. 84, 3829–3837 (2003)

    Article  CAS  Google Scholar 

  15. Dubochet, J. et al. Cryo-electron microscopy of vitrified specimens. Q. Rev. Biophys. 21, 129–228 (1988)

    Article  CAS  Google Scholar 

  16. Frank, J. Averaging of low exposure electron micrographs of non-periodic objects. Ultramicroscopy 1, 159–162 (1975)

    Article  CAS  Google Scholar 

  17. Frank, J. Classification of macromolecular assemblies studied as ‘single particles’. Q. Rev. Biophys. 23, 281–329 (1990)

    Article  CAS  Google Scholar 

  18. Seeman, N. C. & Kallenbach, N. R. Design of immobile nucleic acid junctions. Biophys. J. 44, 201–209 (1983)

    Article  CAS  Google Scholar 

  19. Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 1–10 (2003)

    Article  Google Scholar 

  20. Stemmer, W. P., Crameri, A., Ha, K. D., Brennan, T. M. & Heyneker, H. L. Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides. Gene 64, 49–53 (1995)

    Article  Google Scholar 

  21. Carragher, B. et al. Leginon: an automated system for acquisition of images from vitreous ice specimens. J. Struct. Biol. 132, 33–45 (2000)

    Article  CAS  Google Scholar 

  22. Ludtke, S. J., Baldwin, P. R. & Chiu, W. EMAN: semiautomated software for high-resolution single-particle reconstructions. J. Struct. Biol. 128, 82–97 (1999)

    Article  CAS  Google Scholar 

  23. Huang, C. C., Couch, G. S., Pettersen, E. F. & Ferrin, T. E. Chimera: An extensible molecular modeling application constructed using standard components. Pacif. Symp. Biocomput. 1, 724 (1996)

    Google Scholar 

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We thank F. Guerra for help with EMAN reconstructions and B. Carragher, R. Milligan and C. Potter for advice on reconstructions. This work was supported by the National Aeronautics and Space Administration and The Skaggs Institute for Chemical Biology at The Scripps Research Institute. Some of the work presented here was conducted at the National Resource for Automated Molecular Microscopy, which is supported by the National Institutes of Health through the National Center for Research Resources. W.M.S. is a Fellow supported by the Damon Runyon Cancer Research Foundation. Molecular graphics images were produced using the UCSF Chimera package.

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Correspondence to William M. Shih.

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Shih, W., Quispe, J. & Joyce, G. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004).

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