Publication: A Look into the Development of Real-Time Shape-Changing DNA Origami
Date
2023-08-03
Authors
Farag, Sally
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Abstract
DNA origami is the art of folding DNA molecules into prescribed nanostructures that may be used as nanocarriers for various applications such as drug and vaccine delivery. These DNA origami structures are assembled with two different types of DNA strands: one long single-stranded DNA scaffold strand, and several short oligonucleotides, called the staple strands. While there have been many advancements in this field, with notably the synthesis of actuatable nanoparticles, little is known on how to design shape-changing DNA origami. This type of structure could be used to trigger specific biological mechanisms by releasing or presenting biomolecules upon specific stimuli such as pH, biomolecules (e.g., RNA or cytokines), or temperature. This research focuses on applying DNA origami design concepts to construct multiple DNA nanoparticles with the same single-stranded scaffold strand. These nanoparticles would only have a few variations in the staple strands used to allow quick shape-changing by replacing only a few strands.
Complex structures of DNA nanoparticles can be assembled with multiple smaller origami structures that act as building-blocks pieced together and can be reorganized to provide fast shape-changes. As such, before designing the final nanoparticle structures in TIAMAT, a tetrahedron was designed to serve as their building-block, allowing for a more cohesive build and transition between each nanoparticle. Through this method, two different nanoparticle structures were designed, each containing three of the tetrahedrons: a triangular structure and a crescent structure. Both were made using the same 1,632 nucleotides scaffold strand, demonstrating that designing multiple structures from the same strand is possible. This allows for a better understanding towards the development of real-time shape-changing DNA origami. The designed structures were folded to observe their ability to transform from one shape to the next, using strand displacement as proof of principle for the occurrence of shape-changes. Various characterization methods were used, including gel electrophoresis, dynamic light scattering (DLS), and atomic force microscopy (AFM) in order to obtain information on the size and shape of the folded structures to confirm whether they folded appropriately and whether shape-change occurred.
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Keywords
DNA origami, shape changing, nanoparticle, nanostructure