Abstract
Broad-spectrum antiviral platforms that can decrease or inhibit viral infection would alleviate many threats to global public health. Nonetheless, effective technologies of this kind are still not available. Here, we describe a programmable icosahedral canvas for the self-assembly of icosahedral shells that have viral trapping and antiviral properties. Programmable triangular building blocks constructed from DNA assemble with high yield into various shell objects with user-defined geometries and apertures. We have created shells with molecular masses ranging from 43 to 925 MDa (8 to 180 subunits) and with internal cavity diameters of up to 280 nm. The shell interior can be functionalized with virus-specific moieties in a modular fashion. We demonstrate this virus-trapping concept by engulfing hepatitis B virus core particles and adeno-associated viruses. We demonstrate the inhibition of hepatitis B virus core interactions with surfaces in vitro and the neutralization of infectious adeno-associated viruses exposed to human cells.
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Data availability
Source data are provided with this paper. The remaining data supporting the findings of this study are available within the paper and its Supplementary Information files, and are available from the corresponding author upon reasonable request. The cryo-EM data from this study have been deposited in the Electron Microscopy Data Bank with the following accession codes: EMD-12007, EMD-12008, EMD-12009, EMD-12010, EMD-12011, EMD-12012, EMD-12013, EMD-12014, EMD-12015, EMD-12016, EMD-12019, EMD-12020, EMD-12021, EMD-12022, EMD-12023, EMD-12024, EMD-12044, EMD-12045, EMD-12046 and EMD-12049.
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Acknowledgements
We thank B. Kick for help with the antibody–DNA conjugation and for scaffold preparation. We also thank the Monoclonal Antibody Facility of Helmholtz Zentrum München (head: R. Feederle) for help with generating and providing anti-HBc 17H7. This work was supported by a European Research Council Consolidator Grant to H.D. (grant no. 724261), the Deutsche Forschungsgemeinschaft through grants provided within the Gottfried-Wilhelm-Leibniz Program and the SFB863 TPA9 (to H.D.), the TRR179 (TP14 to U.P.), the German Ministry for Education and Research (BMBF) through StabVacB and DZIF (project 05.806/907 to U.P.), the European Commission FET Open Grant VIROFIGHT (grant no. 899619 to H.D. and U.P.), the Netherlands Organization for Scientific Research (NWO, Rubicon programme, project no. 019.182EN.037 to W.E.), the USA National Science Foundation through the Brandeis University Materials Research Science and Engineering Center (NSF DMR-1420382 and NSF DMR-2011486 to S.F. and M.F.H.), the National Institute of General Medical Sciences (award no. R01GM108021 to M.F.H.) and the Alexander von Humboldt Foundation (Humboldt Research Fellowship to J.A.K.). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 899619. The views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out.
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Authors and Affiliations
Contributions
H.D. designed the research. S.F. co-designed the icosahedral shell self-assembly studies (Figs. 1 and 2). C.S. performed shell subunit design, shell assembly and all structural studies (Figs. 1–6). E.M.W. performed shell modification and stabilization, and HBV virus-binding inhibition experiments (Figs. 4–6), supported by A.L. W.E. performed subunit exchange and HBV virus-binding inhibition experiments (Figs. 4 and 5). J.A.K. performed the cell culture AAV neutralization experiments (Fig. 6). K.S. performed auxiliary shell subunit geometry alteration experiments (Supplementary Fig. 18). F.K., F.W. and U.P. contributed HBV samples, and generated and provided anti-HBc (Fig. 5). S.A.A. performed cargo encapsulation (Supplementary Fig. 36). M.F.H. contributed to shell design choices.
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A provisional patent has been filed by the TUM (PCT/EP2021/054307).
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Peer review information Nature Materials thanks Xing Wang, Andrew Ward, Hao Yan and Todd Yeates for their contribution to the peer review of this work.
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Supplementary information
Supplementary Information
Supplementary Figs. 1–46, Tables 1–3, Videos 1–8, Note 1 and references.
Supplementary Video 1
Cryo-EM reconstruction of the octahedron shell.
Supplementary Video 2
Cryo-EM reconstruction of the T = 1 shell.
Supplementary Video 3
Cryo-EM reconstruction of the T = 3 shell.
Supplementary Video 4
Cryo-EM reconstruction of the T = 4 shell.
Supplementary Video 5
Slices through a negative stain TEM tomogram of the T = 9 shell.
Supplementary Video 6
Cryo-EM reconstruction of two half octahedral shells + HBV core.
Supplementary Video 7
Cryo-EM reconstruction of two half octahedral shells + HBV core.
Supplementary Video 8
Cryo-EM reconstruction of the spiky T = 1 shell.
Supplementary Data
DNA sequences of staple strands.
Source data
Source Data Fig. 3
Uncropped gel scans.
Source Data Supplementary Fig. 11
Uncropped gel scans.
Source Data Supplementary Fig. 22
Uncropped gel scans.
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Sigl, C., Willner, E.M., Engelen, W. et al. Programmable icosahedral shell system for virus trapping. Nat. Mater. 20, 1281–1289 (2021). https://doi.org/10.1038/s41563-021-01020-4
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DOI: https://doi.org/10.1038/s41563-021-01020-4
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