Toehold-Mediated Shape Transition of Nucleic Acid Nanoparticles

We introduce a toehold-mediated strand displacement strategyforregulated shape-switching of nucleic acid nanoparticles (NANPs) enablingtheir sequential transformation from triangular to hexagonal architecturesat isothermal conditions. The successful shape transitions were confirmedby electrophoretic mobility shift assays, atomic force microscopy,and dynamic light scattering. Furthermore, implementation of splitfluorogenic aptamers allowed for monitoring the individual transitionsin real time. Three distinct RNA aptamers malachite green (MG),broccoli, and mango were embedded within NANPs as reporterdomains to confirm shape transitions. While MG "lights up"within the square, pentagonal, and hexagonal constructs, the broccoliis activated only upon formation of pentagon and hexagon NANPs, andmango reports only the presence of hexagons. Moreover, the designedRNA fluorogenic platform can be employed to construct a logic gatethat performs an AND operation with three single-stranded RNA inputsby implementing a non-sequential polygon transformation approach.Importantly, the polygonal scaffolds displayed promising potentialas drug delivery agents and biosensors. All polygons exhibited effectivecellular internalization followed by specific gene silencing whendecorated with fluorophores and RNAi inducers. This work offers anew perspective for the design of toehold-mediated shape-switchingnanodevices to activate different light-up aptamers for the developmentof biosensors, logic gates, and therapeutic devices in the nucleicacid nanotechnology.