Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

VLPs such as the brome mosaic virus, CCMV, papillomavirus and polyomavirus have been used to package and deliver exogenous DNAs. 83 Pan et al. 1 used bacteriophage MS2 VLPs to deliver human pre-miRNA. The nanocages were simultaneously decorated with cellpenetrating peptides and transactivator of transcription 47-57 to enhance cellular penetration. The designed delivery vehicle promotes subcellular localization of nucleic acid miR-146a, which suppresses the target gene effectively. 1 Small interfering RNA encapsulated in HBV capsid nanocarriers was shown to systemically deliver small interfering RNA to cancer sites in mice and effectively silences the target gene. 84 Protein nanocages have also been explored as carriers for protein-based therapeutics. Delivery of protein therapeutics requires protein nanocages with larger cavities. Model therapeutic molecules, such as prodrugs and enzymes, have been packaged in VLPs by fusing them to Gag proteins. 85 Viral vectors are naturally taken up by cells through the interaction of the envelope protein on their outer surface with cell receptors. 1 VSV-G envelope 86 or other localizing targeting ligands further increase the efficiency of delivery of the cargos to particular cells. Vaults with a volume of~122,000 nm 3 are good non-viral protein nanocages candidates for packaging of protein-based therapeutics 26 . Loading can be facilitated by fusing the protein of interest with INT, which serves as a shuttle protein to package the molecule inside the vault. 27 Modifications of the vault interior and exterior to accommodate other therapeutics or other ligands are reviewed in other sections.