Protein Nanocages as Building Blocks for Conjugated Supramolecular Materials Displaying Multitasking Properties

Protein nanocages are a group of compartments naturally enclosing nucleic acids or proteins for biological purposes. Such materials have also inspired the design of novel proteins displaying self-assembling properties. The most studied protein nanocages are viral capsids and their derivative virus-like particles (VLPs), which consist of any or all of the structural proteins of the virion but lack nucleic acids and are therefore non-infectious. VLPs can be used as vaccine antigens or decorated with heterologous antigens to develop new vaccine materials. External surfaces of VLPs can also be decorated with chemical substances to impart new properties, like fluorescence tags or binding to cellular receptors. In addition, the internal space of VLPs can be used to encapsulate therapeutic materials that can be carried to specific cells or tissues. Although VLPs are naturally polyvalent and can display more than one decorating element, it is possible to expand the repertoire of decorating species by specifically conjugating different VLPs, which can be decorated with different functional elements. Here, VLPs of parvovirus B19 displaying different functional proteins were linked through the SpyTag-SpyCatcher biorthogonal conjugation technology. Characterizing the resulting species demonstrated the bioconjugation and the presence of the individual properties of each component. This proof-of-concept research implies that novel multitasking biomaterials can be constructed from protein nanocages and that the application landscape is vast and highly expandable.