DNA-Based Vehicles for the Delivery of Functional Nucleic Acids and Proteins

The ability of DNA to form predictable nanostructures through sequence-directed hybridization has allowed the design of complex supramolecular materials.  Our discovery of the nuclease resistance of DNA nanostructures has led us to explore their potential as delivery vehicles, and we have successfully demonstrated their ability to delivery functional antisense in vitro.  More recently, we have pursued non-canonical Watson-Crick base pairing as an in situ approach for achieving actuation through sensitivity to solution conditions.  By designing a DNA pyramid containing i-motif elements, we have shown that these i-motifs can be used to regulate nanostructure assembly / disassembly as well as the release of protein cargo.  Importantly, disassembly is triggered with physiologically relevant acidification, making the present DNA pyramids an important step towards synthetic mimics of viruses. We are currently exploring the incorporation of aptamer sequences into our pyramids to achieve both targeting and uptake without the need for transfection reagents.