Engineering Protein Cages with Synthetic Biology

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James Field, Geoff Baldwin, Paul Freemont, Richard Kitney

Imperial College London, United Kingdom

Protein nanocages (PNs) are spherically shaped polymeric structures with large internal cavities. In nature, PNs enable nano-scale compartmentalization. Cellular organisms use these nano-scale compartments to sequester toxic species, enhance reaction kinetics, traffic molecules and re-fold proteins. Virally encoded PNs (termed capsids) confer both host specificity and protection during the extracellular phase of their life cycle. The diversity of PNs and their occurrence in all domains of life reflect both the importance of nanoscale compartmentalization and the flexibility of the ‘hollow sphere’ architecture. From a biotechnological perspective, PNs represent an attractive engineering substrate. They are genetically programmable, biocompatible, biodegradable and physically uniform. To rationalize design, we have collated a library of naturally occurring PNs and developed an accompanying suite of in-silico characterisation tools. We hope that this resource will support Synthetic Biologists in their selection and use of PNs for the construction of nano-scale devices. In addition, we demonstrate how PNs can be re-engineered such that their inner cavities can be loaded with different nanoparticles. We are presently investigating how the external surfaces of these hybrid PNs can be functionalized to produce a targeted therapeutic against cholangiocarcinoma.