ABSTRACT
As the emerging field, RNA nanotechnology has brought vitality to the area of therapeutics. Due to its complementary nature of the four nucleotides and the unique property of noncanonical base pairing and stacking, RNA can be manipulated with simplicity characteristic of DNA, while possessing versatile structure and diverse function similar to proteins. There are immersive RNA secondary structure subunits and motifs that have been discovered and thoroughly studied. By rational design, these structure motifs can be utilized as the building block for self-assembly of RNA nanostructures and nanoparticles with special functionalities.
Bacteriophage phi29 DNA packaging motor is geared by a ring consisting of six packaging RNA (pRNA) molecules. pRNA has two interlocking hand-in-hand loops and a three-way junction motif. pRNA nanoparticles have several features that make them attractive delivery platforms: (1) Diverse and stable complex 2D, 3D, and 4D structures; (2) Thermodynamic and enzymatic stability; (3) Complete biocompatibility; (4) Multimodality of different mechanisms of actions in a single particle. These unique features make it an ideal polyvalent vehicle for nanomachine fabrication, pathogen detection, and delivery of siRNA or other therapeutics. This chapter describes methods in using pRNA as a building block for the construction of RNA dimers, trimmers, and hexamers as nanoparticles harboring functional RNA including aptamer, siRNA, ribozyme, chemical ligand, or other regulators for medical applications.
