Three-Dimensional DNA Nanostructures for Biological and Materials Applications

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Our research group focuses on using the biological molecule DNA to achieve programmable organization on the nanometer scale. In the past five years, we have shown simple and efficient methods to construct a range of 3D-DNA cages and nanotubes, with full control of size and shape. These structures can encapsulate cargo and release it in response to specific biological molecules, and they can travel across the plasma membrane of a number of mammalian cells, without the aid of transfection reagents. This proposal seeks to develop a fundamental understanding of how these highly organized DNA nanostructures interact with each other, and with other biological structures. We describe the protein-inspired design of functional DNA structures, whose domains associate together with strategically positioned side-chains. We use supramolecular interactions (hydrophobic, metal coordination, electrostatic, etc.) working together in concert. In addition to introducing complexity into DNA nanotechnology without using hundreds of different DNA sequences, these studies will increase our understanding of the protein folding problem. This work will develop DNA cages that encapsulate small molecule cargo and release it in the presence of a biological trigger, such as mRNA, proteins or molecules in a disease environment, for potential targeted drug delivery. We show a method to transfer the 3D-sequence information from a DNA cage, into crosslinked nanoparticles that are monodisperse and that possess a defined number of DNA arms and orientations. This will lead to a new generation of precisely patterned, functional materials for applications in nanoelectronics, nanooptics and light-harvesting.