期刊
BIOMATERIALS
卷 269, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120650
关键词
Virus-like particles; RNA; Vaccine; Self-assembly; Chaperone
资金
- Ministry of Food and Drug Safety [20173MFDS295-2]
- Korea Health Technology R&D Project through the KoreaHealth Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HV20C0001]
- Brain Korea 21 (BK21) FOUR program
Virus-like particles (VLPs) represent a high-priority vaccine platform against emerging viral infections, with RNA and tRNA playing crucial roles in protein folding and antigen assembly.
Representing highly ordered repetitive structures of antigen macromolecular assemblies, virus-like particles (VLPs) serve as a high-priority vaccine platform against emerging viral infections, as alternatives to traditional cell culture-based vaccines. RNAs can function as chaperones (Chaperna) and are extremely effective in promoting protein folding. Beyond their canonical function as translational adaptors, tRNAs may moonlight as chaperones for the kinetic control of macromolecular antigen assembly. Capitalizing on genomic RNA co-assembly in infectious virions, we present the first report of a biomimetic assembly of viral capsids that was assisted by non-viral host RNAs into genome-free, non-infectious empty particles. Here, we demonstrate the assembly of bacterially-produced soluble norovirus VP1 forming VLPs (n = 180) in vitro. A tRNA-interacting domain (tRID) was genetically fused with the VP1 capsid protein, as a tRNA docking tag, in the bacterial host to transduce chaperna function for de novo viral antigen folding. tRID/tRNA removal prompted the in vitro assembly of monomeric antigens into highly ordered repetitive structures that elicited robust protective immune responses after immunization. The chaperna-based assembly of monomeric antigens will impact the development and deployment of VLP vaccines for emerging and re-emerging viral infections.
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