UC Riverside

Nucleic acid nanotechnology proposes many approaches to construct self-assembled structures using RNA and DNA. These structures have several applications such as scaffolding, sensing, and drug delivery. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties that must be considered when using these molecules to assembly structures. RNA is a natural multifunctional polymer, and has an essential role in complex pathways and structures within the cellular environment. Due to its rich and diverse biological functions, synthetic self-assembling RNA nanostructures are emerging as a powerful tool with potential applications in drug delivery and intracellular control.

Here we demonstrate the formation of RNA nanostructures of varying size, complexity, and biological functionality using methods adapted from DNA nanotechnology. To achieve this goal we imported established approaches in the field of DNA nanostructure and DNA circuit design and optimized assembly protocols to ensure high yield of assembly. We employed design principles and experimental methods to obtain synthetic programmable RNA structures with biological functionality through two primary objectives: (1) Design and characterization of RNA tiles that assemble into RNA nanostructures with predictable features and (2) The usefulness of our RNA assemblies in a biomedical application, in particular functionalization with RNA molecules such as small interfering RNA (siRNA) for targeted RNA interference to inhibit gene expression. Our results show that scalable RNA self-assembled structures can be obtained using purely with Watson-Crick interactions, without relying on conserved tertiary structure motifs typically used to build RNA structures. Lastly, results show that functionalization does not prevent nanostructure assembly and these structures are capable of silencing genes.