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DNA-origami-directed virus capsid polymorphism.

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.

SUBMITTER: Seitz I

PROVIDER: S-EPMC10575778 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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DNA-origami-directed virus capsid polymorphism.

Seitz Iris I Saarinen Sharon S Kumpula Esa-Pekka EP McNeale Donna D Anaya-Plaza Eduardo E Lampinen Vili V Hytönen Vesa P VP Sainsbury Frank F Cornelissen Jeroen J L M JJLM Linko Veikko V Huiskonen Juha T JT Kostiainen Mauri A MA

Nature nanotechnology 20230717 10

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 c ...[more]

PMID: 37460794

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Project description:Directed self-assembly of designed viral capsids holds significant potential for applications in materials science and medicine. However, the complexity of preparing these systems for assembly and the difficulty of quantitative experimental measurements on the assembly process have limited access to critical mechanistic questions that dictate the final product yields and isomorphic forms. Molecular simulations provide a means of elucidating self-assembly of viral proteins into icosahedral capsids and are the focus of the present study. Using geometrically realistic coarse-grained models with specialized molecular dynamics methods, we delineate conditions of temperature and coat protein concentration that lead to the spontaneous self-assembly of T = 1 and T = 3 icosahedral capsids. In addition to the primary product of icosahedral capsids, we observe a ubiquitous presence of nonicosahedral yet highly symmetric and enclosed aberrant capsules in both T = 1 and T = 3 systems. This polymorphism in assembly products recapitulates the scope and morphology of particle types that have been observed in mis-assembly experiments of virus capsids. Moreover, we find that this structural polymorphism in the end point structures is an inherent property of the coat proteins and arises from condition-dependent kinetic mechanisms that are independent of the elemental mechanisms of capsid growth (as long as the building blocks of the coat proteins are all monomeric, dimeric, or trimeric) and the capsid T number. The kinetic mechanisms responsible for self-assembly of icosahedral capsids and aberrant capsules are deciphered; the self-assembly of icosahedral capsids requires a high level of assembly fidelity, whereas self-assembly of nonicosahedral capsules is a consequence of an off-pathway mechanism that is prevalent under nonoptimal conditions of temperature or protein concentration during assembly. The latter case involves kinetically trapped dislocations of pentamer-templated proteins with hexameric organization. These findings provide insights into the complex processes that govern viral capsid assembly and suggest some features of the assembly process that can be exploited to control the assembly of icosahedral capsids and nonicosahedral capsules.

Dataset Information

DNA-origami-directed virus capsid polymorphism.

Publications

DNA-origami-directed virus capsid polymorphism.

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