Protein encapsidation and delivery within recombinant virus-derived protein cages

Protein encapsidation and delivery within recombinant virus-derived protein cages

Presenter: Dr Frank Sainsbury
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Australia

The use of viruses and recombinant virus capsids, or virus-like particles (VLPs), as nanoscale componentry shows great potential in diverse application areas including biocatalysis, immunotherapy and therapeutic delivery. As supramolecular assemblies, VLPs boast unrivalled structural precision, biocompatibility, and benign manufacturing conditions. Owing to the high-resolution structural knowledge that exists for several VLPs, they represent a powerful platform for rational bioengineering by both genetic and chemical means. I will present recent work to control protein encapsidation with two platforms, Bluetongue virus (BTV) core-like particles and Murine Polyomavirus (MPyV) VLPs. Each has a unique set of characteristics that define their suitability to different applications. Determining the structure of BTV cores by Cryo-EM has shown them to be remarkably stable and suited to expression in plant hosts. Unusual colloidal properties points to their potential use as recoverable biocatalytic nanoreactors. The in vitro self-assembly of MPyV VLPs permits the controlled, stoichiometric co-encapsidation of non-covalently anchored cargo proteins. The infection pathway of MPyV is mimicked by VLPs, pointing to use as intracellular protein delivery vehicles. Biophysical techniques such as Förster resonance energy transfer (FRET) between co-encapsidated fluorescent proteins, nanoparticle tracking, and super resolution microscopy has shed light onto the co-operative self-assembly process of VLPs and the impact of encapsidating protein cargo on self-assembly.