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Acknowledgements

We thank N. Ponnuswamy, R. Sørensen, J. Hahn, J. Lara, L. Chou, N. Garreau, S. Saka, H. Sasaki, J. B. Woehrstein and C. B. Marks for experimental help. We also thank B. Wei, W. Sun and W.M. Shih for discussions, M. Beatty and J. Cheng for help in developing the Nanobricks platform, and C. Chen for assistance with draft preparation. The work was funded by Office of Naval Research grants N000141010827, N000141310593, N000141410610, N000141612182 and N000141612410, an Army Research Office grant W911NF1210238, National Science Foundation grants CCF-1054898, CCF-1162459, CCF-1317291, CMMI-1333215, CMMI-1334109 and CMMI-1344915, an Air Force Office of Scientific Research grant AFA9550-15-1-0514, and National Institute of Health grants 1DP2OD007292 and 1R01EB018659, 167814 (P.Y.); an Emory Biomedical Engineering Department Startup Fund, an Emory Winship Cancer Institute Billi and Bernie Marcus Research Award, a Winship Cancer Institute grant number IRG-14-188-0 from the American Cancer Society, and a National Science Foundation CAREER Award DMR–1654485 (Y.K.); French National Research Agency grants ANR-16-CE09-0004-01 and ANR-15-CE09-0003-02 (G.B.); and a French National Research Agency grant ANR-10-INBS-05 (P.B.). L.L.O. was funded by an NSF graduate research fellowship. N.H. was funded by the German National Academic Foundation and German Academic Exchange Service. M.T.S. acknowledges support from the International Max Planck Research School for Molecular and Cellular Life Sciences (IMPRS-LS).

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Authors and Affiliations

  1. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, 02115, Massachusetts, USA
    Luvena L. Ong, Nikita Hanikel, Omar K. Yaghi, Casey Grun, Maximilian T. Strauss, Florian Schueder, Bei Wang, Jocelyn Y. Kishi, Cameron Myhrvold, Allen Zhu & Peng Yin
  2. Harvard–MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA
    Luvena L. Ong
  3. Max Planck Institute of Biochemistry, Martinsried Munich, 82152, Germany
    Maximilian T. Strauss, Florian Schueder & Ralf Jungmann
  4. Department of Physics and Center for Nanoscience, Ludwig Maximilian University, Munich, 80539, Germany
    Maximilian T. Strauss, Florian Schueder & Ralf Jungmann
  5. Centre de Biochimie Structurale, CNRS UMR 5048, INSERM U1054, Montpellier, F-34000, France
    Patrick Bron & Josephine Lai-Kee-Him
  6. Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China
    Bei Wang
  7. Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, 30322, Georgia, USA
    Pengfei Wang & Yonggang Ke
  8. Department of Systems Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Jocelyn Y. Kishi, Cameron Myhrvold & Peng Yin
  9. Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U1191, Montpellier, F-34000, France
    Gaetan Bellot
  10. Department of Chemistry, Emory University, Atlanta, 30322, Georgia, USA
    Yonggang Ke

Authors

  1. Luvena L. Ong
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  2. Nikita Hanikel
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  3. Omar K. Yaghi
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  4. Casey Grun
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  5. Maximilian T. Strauss
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  6. Patrick Bron
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  7. Josephine Lai-Kee-Him
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  8. Florian Schueder
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  9. Bei Wang
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  10. Pengfei Wang
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  11. Jocelyn Y. Kishi
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  12. Cameron Myhrvold
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  13. Allen Zhu
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  14. Ralf Jungmann
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  15. Gaetan Bellot
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  16. Yonggang Ke
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  17. Peng Yin
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Contributions

L.L.O. conceived the project, designed and performed the experiments, analysed the data and wrote the paper. N.H. designed and performed the experiments, analysed the data and wrote the paper. O.K.Y., B.W. and P.W. performed the experiments and analysed the data. M.T.S. and F.S. performed the 3D DNA-PAINT experiments, analysed the data and wrote the paper. C.G. and J.Y.K. developed the Nanobricks software and wrote the paper. P.B. and J.L.-K.-H. performed the electron tomography experiments. C.M. designed and analysed the sequencing experiments and wrote the paper. A.Z. performed the experiments. R.J. supervised the DNA-PAINT experiments, interpreted data and wrote the paper. G.B. designed and supervised the electron tomography study, interpreted data and wrote the paper. Y.K. and P.Y. conceived, designed and supervised the study, interpreted the data and wrote the paper.

Corresponding authors

Correspondence toGaetan Bellot, Yonggang Ke or Peng Yin.

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Competing interests

A patent has been filed based on this work. P.Y. is co-founder of Ultivue Inc. and NuProbe Global.

Additional information

Reviewer Information Nature thanks C. Lin and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Extended data figures and tables

Extended Data Figure 1 Gel electrophoresis analysis of DNA brick cuboids.

ah, Structures of varying size (see schematics on the left) were assembled isothermally for 5–7 days at the temperatures indicated above each gel lane, with strand concentrations of 30 nM (ad), 5 nM (e, g), 3 nM (f) and 20 nM (h). The number below each lane indicates the formation yield of the target structure. Lane ‘M’ contains a 1-kilobase ladder.

Extended Data Figure 2 Characterization of 30H × 30H × 260B cavity shapes.

a, Schematic of the 30H × 30H × 260B molecular canvas (grey) compared with a DNA-origami-sized structure (blue). b, For each structure (numbered 1–7), the top panels show 3D models of the designed structure, the bottom left panels show expected TEM projections and the bottom right panels show the TEM averages from at least six particles. c, The structures were folded with 5 nM per strand by isothermal annealing or by using a narrow ramp from 52.5 °C to 51 °C. Products were analysed on a 0.5% agarose gel in the presence of 10 mM MgCl2. The percentage listed below a target band indicates the gel yield; labels correspond to those in b or in Fig. 3.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Data, Supplementary Tables 1-3, Supplementary Figures 1-113 and Supplementary References – see contents pages for details. (PDF 30485 kb)

Supplementary Data 1

This file contains the sequences used for each structure on separate tabs. (XLSX 4706 kb)

Bear structure

Tomography video of the bear structure (AVI 11680 kb)

GEB structure

Tomography video of the GEB structure (AVI 12801 kb)

Helix structure

Tomography video of the helix structure (AVI 7636 kb)

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Ong, L., Hanikel, N., Yaghi, O. et al. Programmable self-assembly of three-dimensional nanostructures from 10,000 unique components.Nature 552, 72–77 (2017). https://doi.org/10.1038/nature24648

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