Figure 4.

Examples of GalNAc Clusters in Use in Preclinical and Clinical Studies

Blue branches and circles are GalNAc clusters, green circles are 2′-fluoro nucleotides, yellow circles are 2′-O-methyl nucleotides, brown circles are 2′-methoxyethyl nucleotides, dark gray circles are bridged nucleic acids (LNA/cEt), white circles are DNA nucleotides, red circles are 5′-vinyl phosphonate, and light gray circles are either 2′-fluoro or 2′-O-methyl nucleotides. (A) siRNA GalNAc conjugate with a triantennary cluster (Alnylam). (B) siRNA GalNAc conjugate with sequential GalNAc on a tetraloop (Dicerna). (C) MOE Gapmer GalNAc conjugate with a triantennary cluster (IONIS, second generation). (D) LNA Gapmer GalNAc conjugate with a sequential cluster (Yamamoto). (E) Anatomy of a GalNAc cluster.