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Self-assembly of DNA into nanoscale three-dimensional shapes

An Erratum to this article was published on 25 June 2009

Abstract

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.

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Acknowledgements

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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The authors declare competing financial interests: details accompany the paper on www.nature.com/nature.

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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). https://doi.org/10.1038/nature08016

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