The nucleic acid side chains extending from the sugar-phosphate backbone form hydrogen bonds between the nucleic acid bases of complementary RNA chains; U bonds with A, and G bonds with C. Double-stranded RNA structures form as a result of intramolecular and intermolecular base pairing. Base pairing between loops of double-stranded stem-loops can yield 3D structures and triple helixes can form within single strands or between multiple strands. Chemical modifications on RNA can improve the stability and reduce the immunogenicity of therapeutic RNAs. RNA is very susceptible to nucleases and hydrolysis by basic compounds. Chemical modification of RNA protects the vulnerable sugar-phosphate backbone from nuclease degradation and lowers the risk of off-target effects. For RNAs that form a duplex with a target sequence, mutations that lower the melting temperature of the duplex destabilize the complex and improve target specificity by decreasing base pairing with non-target RNA. RNA modifications can also improve the delivery of the RNA into the cell through the plasma membrane and enhance the activity of the RNA.