Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

Constant efforts are being made to engineer natural protein sequences to impart new or additional functions. Recent studies have taken the efforts to a higher level by creating self-assembling protein structures through de novo design. The assembly of small peptides occurs through various non-covalent interactions, van der Waals, hydrophobic, π-π staking, electrostatic interactions, hydrogen bonds and disulfide bond formation. 1 On the smallest possible scale, small proteins that self-assemble to form helical bundles consisting of two to four helices are designed by focusing on simple folding patterns, particularly the α-helices or coiled-coil arrangements. 32 The phenomenon of biological self-assembly observed in amyloidogenesis, in which a soluble protein is transformed into insoluble aggregates (amyloid fibrils) by a chemically specific molecular assembly process involving domain swapping and symmetric oligomerization, could be considered the inspiration in designing artificial supramolecular protein structures. 32 Stringing multiple protein domains to construct modular proteins allows for the incorporation of multiple functions into a single polypeptide chain. The modular protein has been used for in vitro condensation and targeted cell delivery of nucleic acids. 1 This novel approach has paved the way to designing a variety of protein/DNA complexes to deliver nucleic acid therapeutics both in vitro and in vivo.