Atomic Structure of the World's Smallest Virus-Like Particles: Pleasant Surprises in Clinical Applications
Conference Contribution ResearchOnline@JCUAbstract
There is a growing need to enhance our capabilities in tackling numerous issues regards to human and animal health. Virus-like particles (VLPs) possess numerous features that make them well-suited for use in targeted delivery of therapeutic agents, vaccine development and diagnostics. However, little effort has been given to the use of VLPs for the targeted delivery and trafficking of functional cargo, even though they possess several features that make them attractive as potential nanocarriers. Here we describe the world's smallest known VLPs, which self-assemble from a circovirus, beak and feather disease virus (BFDV) capsid-protein, a virus known not to infect mammals. We have solved the VLPs structure by a combination of x-ray crystallography and Cryo-EM; The 17 nm assemblies comprised 60 Cap monomers in the absence and presence of single-stranded DNA (ssDNA), and where determined to 2.5 Å and 2.3 Å resolution respectively, in the same space group, arranged as 12 pentamers. Furthermore using in vitro studies, we show that BFDV VLPs can bind and deliver fluorescently-labelled non-specific nucleic acids to HeLa and astrocyte cell lines. This VLP-based delivery system may facilitate novel avenues for the targeted delivery of therapeutic drugs, including siRNA for human diseases. Besides, we show that this VLPs can be used in diagnostics assay and development of a recombinant vaccine offering promising results that could lead to the development of strategies for the prevention of a deadly viral infection in the most critically endangered Australian avifauna.
Journal
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Publication Name
The FASEB Journal
Volume
35
ISBN/ISSN
0892-6638
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Pages Count
2
Location
Online
Publisher
John Wiley & Sons
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EISSN
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DOI
10.1096/fasebj.2021.35.S1.00234