ABSTRACT

RNA nanotechnology has recently emerged as a versatile platform for bottom-up fabrication of RNA nanoparticles with desired structure and stoichiometry. RNA possesses many intrinsic nanoscale attributes, which make it particularly attractive as a construction material. It can be designed and manipulated as simply as DNA, while possessing diverse functions and catalytic activity similar to proteins. RNA junctions represent important branched architectural elements that are abundant in many structured RNAs, such as ribosomal RNA (rRNA), transfer RNA (tRNA), ribozymes, and riboswitches. A wide assortment of RNA three-way junction (3WJ) and four-way junction (4WJ) motifs is available for constructing diverse RNA nanoparticles with desired structure and function. Using junction scaffolds, RNA nanoparticles composed of multiple RNA building blocks can be generated by self-assembly to escort siRNA, miRNA, ribozyme, aptamer, or other therapeutics to specific cells. The focus of this chapter is on the use of 3WJ and 4WJ motifs for constructing multivalent RNA nanoparticles for therapeutic and diagnostic applications. The approach relies on utilizing modular building blocks (three–six pieces of RNA oligos) to self-assemble into larger nanoparticles using the bottom-up approach of nanotechnology.