DNA nanotechnology has emerged as an exceptionally programmable method to organize materials. Most current strategies rely on assembling a complex DNA scaffold, often containing hundreds of different strands, and using it to position materials into the desired functional structure. Our research group has developed a different approach to build DNA nanostructures. Starting from a minimum number of DNA components, we create 3D-DNA host structures, such as cages, nanotubes and spherical nucleic acids, that are promising for targeted drug delivery. These can encapsulate and selectively release drugs and materials, and accomplish anisotropic organization of metal nanoparticles and polymers.
We find that they resist nuclease degradation, silence gene expression to a significantly greater extent than their component oligonucleotides and have a favorable in vivo distribution profile. We designed a DNA cube that recognizes a cancer-specific gene product, unzips and releases drug cargo as a result, thus acting as a conditional drug delivery vehicle; as well as DNA structures that bind to plasma proteins with low nanomolar affinities, thus increasing stability in vivo. We will also describe a method to ‘print’ DNA patterns onto other materials, thus beginning to address the issue of scalability for DNA nanotechnology. Finally, we will discuss the ability of small molecules to reprogram the assembly of DNA, away from Watson-Crick base-pairing and into new motifs.