siRNAs have a moderate number of phosphorothioate linkages, with 2'-fluoro and 2'-O-methyl modification of the ribose and are often modified on their 3' ends. The three approved therapeutic siRNAs, Leqvio, Givlaari/Girosiran, and Oxlumo, are 3'-glycosylated with the trivalent GalNAc conjugate 266 shown in Figure . This trivalent branched linker containing GalNAc residues targets the siRNAs to hepatocytes to treat liver diseases. The other approved siRNA, Onpattro, has two 3'-terminal thymidine (dT) residues on both RNA strands to protect the siRNA from exonucleases.