Core–Shell and Layer‐by‐Layer Assembly of 3D DNA Crystals

A long‐standing goal of DNA nanotechnology has been to assemble 3D crystals to be used as molecular scaffolds. The DNA 13‐mer, BET66, self‐assembles via Crick–Watson and noncanonical base pairs to form crystals. The crystals contain solvent channels that run through them in multiple directions, allowing them to accommodate tethered guest molecules. Here, the first example of biomacromolecular core–shell crystal growth is described, by showing that these crystals can be assembled with two or more discrete layers. This approach leads to structurally identical layers on the DNA level, but with each layer differentiated based on the presence or absence of conjugated guest molecules. The crystal solvent channels also allow layer‐specific postcrystallization covalent attachment of guest molecules. Through controlling the guest‐molecule identity, concentration, and layer thickness, this study opens up a new method for using DNA to create multifunctional periodic biomaterials with tunable optical, chemical, and physical properties.