DNA Origami Nanostructures for the Delivery and Discovery of Nucleic Acids
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Date
2017-05
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The Ohio State University
Abstract
Scaffolded DNA origami is a novel DNA-based nanostructure fabrication method that boasts the advantages of ease of fabrication, high customizability in terms of geometry and modifications, and low cytotoxicity, making it an ideal candidate for biological applications. Several groups have already demonstrated its functionality as a drug delivery vehicle, delivering small molecule chemotherapeutics and proteins both in vitro and in vivo. However, the field is far from saturated, and many applications of these devices remain relatively unexplored. One such avenue within the scope of drug delivery is the delivery of antisense therapy, which is showing increasing promise in combating dysregulation of novel targets such as microRNA within disease states. Another approach is to expand the functionality of these nanostructures in biological systems to include the discovery of new interacting partners with ligands, such as microRNA, associated with the nanostructure. The purpose of this work is to expand the field of DNA origami into these fields. In the first project, nanostructures functionalized with sequences antisense to oncogenic microRNA on the outer surface were successfully fabricated. These structures were shown to successfully sequester their target microRNA selectively in solution, and could enter cells without any need of modification. Finally, preliminary data was collected suggesting that the amount to structures within cells can be quantified, and that these structures retain their functionality and are able to affect downstream processes in vitro. In the second project, a process schematic was developed to identify and extract ciRS-7, a circular RNA that strongly interacts with miRNA-7. Structures with overhangs containing the miDNA-7 sequence and a mechanism for binding to, and being released from streptavidin coated beads were successfully synthesized. Each step of the target discovery protocol was validated independently in solution.
This work will hopefully serve as both a basis for optimizing the methods and concepts included within, and as inspiration for the development of novel concepts that take the field even further beyond.
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Keywords
DNA Nanotechnology, Drug Delivery, Cancer, Target Discovery, Process Development