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Issue 4, 2020
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Truncated tetrahedral RNA nanostructures exhibit enhanced features for delivery of RNAi substrates

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Abstract

Using RNA as a material for nanoparticle construction provides control over particle size and shape at the nano-scale. RNA nano-architectures have shown promise as delivery vehicles for RNA interference (RNAi) substrates, allowing multiple functional entities to be combined on a single particle in a programmable fashion. Rather than employing a completely bottom-up approach to scaffold design, here multiple copies of an existing synthetic supramolecular RNA nano-architecture serve as building blocks along with additional motifs for the design of a novel truncated tetrahedral RNA scaffold, demonstrating that rationally designed RNA assemblies can themselves serve as modular pieces in the construction of larger rationally designed structures. The resulting tetrahedral scaffold displays enhanced characteristics for RNAi-substrate delivery in comparison to similar RNA-based scaffolds, as evidenced by its increased functional capacity, increased cellular uptake and ultimately an increased RNAi efficacy of its adorned Dicer substrate siRNAs. The unique truncated tetrahedral shape of the nanoparticle core appears to contribute to this particle's enhanced function, indicating the physical characteristics of RNA scaffolds merit significant consideration when designing platforms for delivery of functional RNAs via RNA nanoparticles.

Graphical abstract: Truncated tetrahedral RNA nanostructures exhibit enhanced features for delivery of RNAi substrates

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Supplementary files

Article information


Submitted
23 Sep 2019
Accepted
20 Dec 2019
First published
14 Jan 2020

Nanoscale, 2020,12, 2555-2568
Article type
Paper

Truncated tetrahedral RNA nanostructures exhibit enhanced features for delivery of RNAi substrates

P. Zakrevsky, W. K. Kasprzak, W. F. Heinz, W. Wu, H. Khant, E. Bindewald, N. Dorjsuren, E. A. Fields, N. de Val, L. Jaeger and B. A. Shapiro, Nanoscale, 2020, 12, 2555
DOI: 10.1039/C9NR08197F

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