Proteins and nucleic acids embody nature’s diversity of function and constitute the majority of machines on this planet. Considering the broad range of tasks natural proteins perform, it stands to reason that developing our own set of nanomachines could solve technical challenges within all branches of science, medicine and technology. While we can now design some protein structures from scratch, function is still elusive. Alternatively, intricate devices can be created using DNA/RNA as a construction material, but many require biologically incompatible assembly conditions, give low yields, exhibit assembly errors and lack robustness. To overcome these limitations and expedite the production of bionanomaterials that can serve practical applications, innovative and economical approaches are still needed.
DNA-based self-assembly is successful due to its highly predictable and easily programmable four-letter code. However, the approach is also limited by this very simplicity. In the first part of my talk, methods to expand DNA nanotechnology beyond the four canonical nucleotides, through protein-inspired synthetic modifications, will be introduced. Specific examples of how this strategy can provide access to unprecedented modes of self-assembly and functionality will be highlighted.
The genetic programmability of proteins enables rational manipulation of existing scaffolds, de novo design of completely novel structures and laboratory evolution of practical properties. Of the natural protein assemblies, well-defined, hollow capsules have proven to be particularly useful due to their ability to compartmentalize macromolecules and chemical processes. Viruses are an important example, as they are the most abundant biological entities on Earth, and are intrinsically tied to complex life and its evolution across all domains. In the second part of my talk, approaches to recapitulate viromimetic function in protein cages of nonviral origin will be described. This bottom-up recreation of virus-like behaviour through protein cage engineering can aid in our understanding of viral origins, evolution and molecular mechanisms, while providing safe alternatives for biomedical applications.