RNA has emerged as important nanotechnology platform due to its diversity and versatility in structure and function.RNA nanoparticles can be made with simplicity characteristic of DNA, while possessing adaptable tertiary structure and catalytic functions that mimic proteins.In comparison to DNA, RNA has higher thermodynamic stability, ability to form non-canonical base pairing and stacking, as well as distinctive in vivo attributes.We have constructed an assortment of thermodynamically and chemically stable RNA nanoparticles carrying multiple therapeutic moieties.These nanoparticles self-assemble efficiently,are resistant to denaturing (boiling, RNase, urea), and remain intact after injection into the body.Each arm of the RNA helices can harbor one siRNA, miRNA, ribozyme, or aptamer without affecting the folding of RNA core, nor that of each daughter therapeutic RNA molecule.Gene silencing effects have been found to progressively enhance as the number of siRNA in each pRNA nanoparticle has been gradually increased.Systemic injection in mice for biodistribution assay of the ligand-containing nanoparticles has revealed that RNA nanoparticles remained intact without showing any signs of dissociation or degradation and strongly bound to tumors without accumulation in other organs or tissues.Pharmacokinetic (PK) analysis has revealed that its half-life has been extended 10-fold, as compared to siRNAs.Particles tested in vivo did not induce cytokines,interferon, antibody and toxicity, and retained favorable PK profiles.