DNA nanotechnology can assemble materials on the nanoscale with exceptional predictability and programmability. In a sense, this field has reduced the self-assembly space into a simple ‘language’ composed of four letters (A, T, G, C). Nature, on the other hand, relies on many more supramolecular interactions or ‘languages’ to build its functional structures. Over the last 50 years, supramolecular chemistry has taken advantage of these interactions to assemble materials with highly diverse structures and functions. This talk will describe our most recent efforts to merge the field of supramolecular chemistry with DNA nanotechnology. This approach results in new motifs and functionalities that are unavailable with base-pairing alone. Starting from a minimum number of DNA components, we create 3D-DNA host structures, such as cages and nanotubes that are promising for targeted drug delivery. These can encapsulate and selectively release drugs and materials, and accomplish anisotropic 3D-organization. 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. 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.

DNA nanostructures for cellular delivery of therapeutics

256th National Meeting (2018)

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