Natural and artificial protein cages: design, structure and therapeutic applications

- Structural analysis of icosahedral and non-icosahedral viral capsids using advanced cryo-electron microscopy techniques.
- Advances in subtomogram averaging have allow high resolution imaging of virus proteins.
- Modification of VLPs to improve pharmacokinetics.
- External and internal modification/cargo capture of VLPs can produce effective vaccines.
- Designing artificial cage by learning from viral capsid structures and using new in silico techniques.

Advanced electron microscopy techniques have been used to solve many viral capsid structures. The resulting detailed structural knowledge contributes to understanding of the mechanisms of self-assembly, maturation pathways and virion-host cell interactions. It also acts as inspiration for design and production of capsid-like artificial protein cages. Both natural and artificial cages have potential uses in medicine including as vaccines and in drug delivery. For vaccines, virus-like particles formed only from outer virion shells, lacking genetic material, offer the simplest basis for development, while encapsulation of target molecules inside protein cages is potentially more challenging. Here we review advances in cryo-electron microscopy with particular reference to viral capsid structures. We then consider why knowledge of these structures is useful, giving examples of their utilization as encapsulation and vaccine agents. Finally we look at the importance of structural techniques including cryo-EM in the rapidly progressing field of designed protein cages.