DNA-origami-directed virus capsid polymorphism

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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en

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8

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Nature Nanotechnology, Volume 18, issue 10, pp. 1205-1212

Abstract

Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. Importantly, precise control over the size and shape of virus capsids would have advantages in the development of new vaccines and delivery systems. However, current tools to direct the assembly process in a programmable manner are exceedingly elusive. Here we introduce a modular approach by demonstrating DNA-origami-directed polymorphism of single-protein subunit capsids. We achieve control over the capsid shape, size and topology by employing user-defined DNA origami nanostructures as binding and assembly platforms, which are efficiently encapsulated within the capsid. Furthermore, the obtained viral capsid coatings can shield the encapsulated DNA origami from degradation. Our approach is, moreover, not limited to a single type of capsomers and can also be applied to RNA–DNA origami structures to pave way for next-generation cargo protection and targeting strategies.

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| openaire: EC/H2020/101002258/EU//ProCrystal Funding Information: The authors acknowledge financial support from the European Research Council (ERC) and ERA Chair MATTER under the European Union’s Horizon 2020 research and innovation programme (grant agreement numbers 101002258 (M.A.K.) and 856705 (V. Linko)), the Emil Aaltonen Foundation (V. Linko), the Sigrid Jusélius Foundation (V. Linko), the Academy of Finland (grant numbers 341057 (E.A.-P.) and 314671 (M.A.K)), the Finnish Foundation for Technology Promotion (V. Lampinen), and the Jane and Aatos Erkko Foundation (V. Linko and M.A.K.). This work was carried out under the Academy of Finland Centers of Excellence Program (2022-2029) in Life-Inspired Hybrid Materials (LIBER), project number number 346110 (M.A.K.). K. M. Nguyen and A. Kuzyk are acknowledged for providing the staple strands for the 13HR sample, P. Laurinmäki and B. Löflund for technical assistance with cryo-EM, M. Hankaniemi for support with NoV production, and M. Sammalkorpi and A. Scacchi for technical discussions. The facilities and expertise of the HiLIFE cryo-EM unit at the University of Helsinki, a member of Instruct-ERIC Centre Finland, FINStruct and Biocenter Finland are gratefully acknowledged. The authors also acknowledge CSC–IT Center of Science, Finland, for computational resources, Biocenter Finland for support of protein production and characterization infrastructure, and the provision of facilities and technical support by Aalto University Bioeconomy Facilities, OtaNanoNanomicroscopy Center (Aalto-NMC) and Micronova Nanofabrication Center. Publisher Copyright: © 2023, The Author(s).

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Seitz, I, Saarinen, S, Kumpula, E-P, McNeale, D, Anaya-Plaza, E, Lampinen, V, Hytönen, V P, Sainsbury, F, Cornelissen, J J L M, Linko, V, Huiskonen, J T & Kostiainen, M A 2023, 'DNA-origami-directed virus capsid polymorphism', Nature Nanotechnology, vol. 18, no. 10, pp. 1205-1212. https://doi.org/10.1038/s41565-023-01443-x