Design Verification as Foundation for Advancing DNA Nanotechnology Applications

Advances in the field of structural DNA nanotechnology have produced a growing number of nanostructures that are now being developed for diverse applications. Often, these nanostructures contain not only nucleic acids but also a myriad of other classes of molecules and materials such as proteins, lipids, sugars, and synthetic polymers. Increasing structural and compositional complexity promises new functional capabilities, but also demands new tools for design verification. Systematically verifying the design of DNA-scaffolded nanomaterials is necessary to identify and to refine their design rules, and to enable the field to progress toward “real world” applications. In this issue of ACS Nano, Bertosin et al. used single-particle cryo-electron microscopy to characterize the structure of multilayer DNA origamis following coating with oligolysine-based polymers, a class of material which has previously been shown to stabilize DNA nanostructures in physiological environments for use in biological applications. This Perspective summarizes their findings, discusses the broader challenges of verifying the design of DNA nanotechnologies incorporating complex materials, and highlights future directions for advancing their applications.