Year: 2023
Type: article
Abstract: We introduce a toehold-mediated strand displacement strategy for regulated shape-switching of nucleic acid nanoparticles (NANPs) enabling their sequential transformation from triangular to hexagonal architectures at isothermal conditions. The successful shape transitions were confirmed by electrophoretic mobility shift assays, atomic force microscopy, and dynamic light scattering. Furthermore, implementation of split fluorogenic aptamers allowed for monitoring the individual transitions in real time. Three distinct RNA aptamers─malachite green (MG), broccoli, and mango─were embedded within NANPs as reporter domains to confirm shape transitions. While MG "lights up" within the square, pentagonal, and hexagonal constructs, the broccoli is activated only upon formation of pentagon and hexagon NANPs, and mango reports only the presence of hexagons. Moreover, the designed RNA fluorogenic platform can be employed to construct a logic gate that performs an AND operation with three single-stranded RNA inputs by implementing a non-sequential polygon transformation approach. Importantly, the polygonal scaffolds displayed promising potential as drug delivery agents and biosensors. All polygons exhibited effective cellular internalization followed by specific gene silencing when decorated with fluorophores and RNAi inducers. This work offers a new perspective for the design of toehold-mediated shape-switching nanodevices to activate different light-up aptamers for the development of biosensors, logic gates, and therapeutic devices in the nucleic acid nanotechnology.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Health and Human Services, University of Nebraska Medical Center, Frederick National Laboratory for Cancer Research, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Division of Materials Research, Division of Biological Infrastructure
Awards: G1536932371, G1979031094, G3503792436, Collaborative Research: Exploring self-organization of functional nucleic acid supramolecular assemblies with stimuli responsive properties, G386607036, G4585269469, G4988656331, G5262810016, G5888954722, Research Infrastructure: MRI: Acquisition of a Biomolecular Imaging System for Research and Education, G8453374444, SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses, Nucleic Acid Nanoparticle-based Monoclonal Antibody Mimics
OpenAlex ID: W4377091049