Design and applications of DNA self-assembled nanoarchitectures and self-replication of DNA origami tiles

Abstract

DNA nanotechnology, first laid out by Nadrian C. Seeman in 1982, is the design and manufacture of artificial DNA nanostructures for technological applications. Because of its self-assembly nature, DNA is an excellent candidate for creating predictable and programmable nanoarchitectures. A variety of fantastic one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) DNA structures have been constructed over the past 30 years, providing all sorts of potential applications. This dissertation focuses on the design and construction of DNA-based materials and their applications. In this dissertation, we first describe a reversible DNA induced hydrogel transition system that could provide a generic strategy for target molecular recognition and separation. We demonstrate that the separation of target molecules can be achieved efficiently without any influence by non-targeted molecules. Second, we indicate the construction of a 3D DNA triangular prism folded from one single-stranded DNA of 198 nucleotides. This is the smallest 3D DNA polyhedron (~3.4 nm) ever reported to the best of our knowledge. The correct assembly of the triangular prism is verified by nondenaturing gel analysis, enzyme digestion, AFM and STM imaging. Third, we develop a self-replicating DNA origami dimer that can undergo exponential amplification indefinitely with sufficient monomer tiles. Moreover, the self-replication of longer DNA origami patterns is also achieved. In addition, we also indicate that the artificial evolution can be realized in a self-replicating fashion by selective self-replication of two competing species using NIR dyes as controlled factors. Finally, we illustrate the design and construction of DNA-based pH-responsive nanogel system for targeted drug delivery. We used aptamer as targeting unit and i-motif transformation in strand G2 as pH-responsive unit. We characterized the nanogel formation by DLS and SEM imaging. The in vitro pH-responsive drug release of the nanogel system is verified by fluorescence spectroscopy. We demonstrate by in vitro anti-proliferation and cellular uptake study that our aptamer-modified DOX-nanogels have better cytotoxicity than free DOX and specific targeting property.

Date of Award	2013
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology