Hybrid Nanostructures from the Self-Assembly of Proteins and DNA

Proteins and DNA are two commonly used molecules for self-assembling nanotechnology. In this tutorial review, we discuss the hybrid field of “protein-DNA nanotechnology,” whereby proteins are integrated with DNA scaffolds for the creation of hybrid nanostructures with distinct properties of each molecular type. We first discuss bioconjugation strategies, both covalent and supramolecular, for integrating proteins with DNA nanostructures. Next, we review seminal work in four emerging areas of protein-DNA nanotechnology: (1) controlling protein orientation on DNA nanoscaffolds, (2) controlling protein function with DNA nanodevices, (3) answering biological questions with protein-DNA nanostructures, and (4) building hybrid structures that integrate both protein and DNA structural units. Finally, we close with a series of forward-looking research propositions and ideas for directions of the field. The emphasis of this work is on integrated nanostructures with precise protein orientation on DNA scaffolds, as well as hybrid assemblies that integrate the structural and functional properties of each molecule.