Virus-Inspired Function in Engineered Protein Cages

The structural and functional diversity of proteins combined with their genetic programmability has made them indispensable modern materials. Well-defined, hollow protein capsules have proven to be particularly useful due to their ability to compartmentalize macromolecules and chemical processes. To this end, viral capsids are common scaffolds and have been successfully repurposed to produce a suite of practical protein-based nanotechnologies. Recently, the recapitulation of viromi-metic function in protein cages of nonviral origin has emerged as a strategy to both complement physical studies of natural viruses and produce useful scaffolds for diverse applications. In this perspective, we review recent progress toward generation of virus-like behavior in nonviral protein cages through rational engineering and directed evolution. These artificial systems can aid our understanding of the emergence of viruses from existing cellular components, as well as provide alternative approaches to tackle current problems, and open up new opportunities, in medicine and biotechnology.