DNA and mRNA origami directed virus capsid polymorphism
Prof. Mauri Kostiainen
Aalto University
Most known viruses protect their genome by encapsulating it inside a protein capsid. Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. The assembly process of native capsids is highly cooperative and governed by the protein geometry, protein-protein as well as protein-nucleic acid interactions. Importantly, the high control over the size and shape of virus capsids would have advantages in the development of new vaccines and delivery systems. However, tools to direct the assembly process in a programmable manner are exceedingly elusive or strictly limited to specific structures. Here, we introduce a modular approach by demonstrating DNA and mRNA origami directed polymorphism of single protein subunit capsids. For the mRNA structures we have identified key folding strategies to enable protein translation, without a separate origami unfolding step. We achieve control over the capsid shape, size, and topology by employing user-defined origami nanostructures as binding and assembly platforms for the capsid proteins. Binding assays and single-particle cryo-electron microscopy reconstruction show that the origami nanoshapes are efficiently encapsulated within the capsid. Further, we observe that helical arrangement of hexameric capsomers is the preferred mode of packing, while a negative curvature of the origami structure is not well tolerated. The capsid proteins assemble on origami in single- or double-layer configurations depending on the applied stoichiometry. In addition, the obtained viral capsid coatings can efficiently shield the encapsulated origami from nuclease degradation and promote transfection. Our approach is, moreover, not limited to a single type of virus capsomers and can also be applied to e.g. pentameric polyoma virus capsid proteins.
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. DNA Origami Directed Virus Capsid Polymorphism, Nature Nanotechnology, 2023, 18, 1205-1212. (https://doi.org/10.1038/s41565-023-01443-x)
Seitz, I.; Sharon, S.; Wierzchowiecka, J.; Cornelissen, J. J. L. M.; Linko, V.; Kostiainen, M. A. Folding of mRNA-DNA Origami for Controlled Translation and Viral Vector Packaging, Advanced Materials, 2025, 2417642. (https://doi.org/10.1002/adma.202417642)
Bio
Mauri Kostiainen obtained his M.Sc. in organic chemistry from the University of Helsinki (2005), and the subsequent Ph.D. in engineering physics from the Helsinki University of Technology (2008). Afterwards he spent 2.5 years as a postdoctoral fellow at the Institute for Molecules and Materials (Radboud University Nijmegen) developing new approaches for chemical and physical virology. He joined the faculty of School of Chemical Engineering at Aalto University (Finland) in 2013. Currently, he is a professor in polymer technology, with research interests focusing on the integration of biological and synthetic building blocks in a designed manner to create biohybrid materials. Of special interest are virus particles and other protein cages that can be repurposed for materials science and biotechnology applications.
