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

Nature volume 427, pages 618621 (12 February 2004) | Download Citation

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Abstract

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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Acknowledgements

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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Affiliations

  1. Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA

    • William M. Shih
    •  & Gerald F. Joyce
  2. Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA

    • Joel D. Quispe

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to William M. Shih.

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https://doi.org/10.1038/nature02307

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