Strategies for Stabilizing DNA Nanostructures to Biological Conditions

DNA is one of the most promising building blocks for creating functional nanostructures for applications in biology and medicine. However, these highly programmable nanomaterials (e.g., DNA origami) often require supraphysiological salt concentrations for stability, are degraded by nuclease enzymes, and can elicit an inflammatory response. Herein, three key strategies for stabilizing DNA nanostructures to conditions required for biological applications are outlined: 1) tuning the buffer conditions or nanostructure design; 2) covalently crosslinking the strands that make up the structures; and 3) coating the structures with polymers, proteins, or lipid bilayers. Taken together, these approaches greatly expand the chemical diversity and future applicability of DNA nanotechnology both in vitro and in vivo.