Protein Cargo Encapsulation by Virus-Like Particles: Strategies and Applications

Viruses and the recombinant protein cages assembled from their structural proteins, known as virus-like particles (VLPs), have gained wide interest as tools in biotechnology and nanotechnology. Detailed structural information and their amenability to genetic and chemical modification make them attractive systems for further engineering. This review describes the range of non-enveloped viruses that have been co-opted for heterologous protein cargo encapsulation and the strategies that have been developed to drive encapsulation. Spherical capsids of a range of sizes have been used as platforms for protein cargo encapsulation. Various approaches, based on native and non-native interactions between the cargo proteins and inner surface of VLP capsids, have been devised to drive encapsulation. Here we outline the evolution of these approaches, discussing their benefits and limitations. Like the viruses from which they are derived, VLPs are of interest in both biomedical and materials applications. The encapsulation of protein cargo inside VLPs leads to numerous uses in both fundamental and applied biocatalysis and biomedicine, some of which are discussed herein. The applied science of protein encapsulating VLPs is emerging as a research field with great potential. Developments in loading control, higher order assembly, and capsid optimization are poised to realize this potential in the near future.