Our research is motivated by the need for stable, nanoparticle-based drug delivery platforms that are composed of nucleotides or nucleotide analogues. Towards this goal, we designed and synthesized site-specifically functionalized DNA origami nanostructures (DONs) using surface-initiated TdT-catalyzed enzymatic polymerization (SI-TcEP). This synergistic combination of surface-initiated enzymatic polynucleotide brush synthesis with precisely engineered DNA origami presents an innovative pathway for the generation of stable, polynucleotide brush functionalized origami nanostructures. Our experimental results show that we have precise control over multiple parameters, including the shape of the origami core, location, height, and composition of the brush. Coarse-grained oxDNA simulation provides us with a powerful tool to design and predict the morphology of origami-brush nanostructures. In addition, we have shown that polynucleotide-functionalized DONs have significantly higher nuclease resistance compared to unprotected DNA origami. Furthermore, this stability can be spatially programmed by designing the positions of the decorating sites on the surface of DONs, potentially allowing the control of the degradation of drug delivery vehicles to facilitate cellular uptake. Together, these attributes will enable new applications of DNA nanotechnology, such as <i>in vivo</i> molecular sensors and smart nanoscale delivery systems.

Programmable site-specific functionalization of DNA origami with polymeric nucleotide brushes

ACS Spring Meeting 2021

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