Inside Cover: 5′‐(E)‐Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA–GalNAc Conjugates (ChemBioChem 11/2016)

The inside cover picture shows the benefit of 5’-(E)-vinylphosphonate (VP), a stable phosphate mimic over 5′-phosphate (5′-P) in improving the siRNA-GalNAc conjugate loading into the RNA-induced silencing complex (RISC). The siRNA conjugated to trivalent N-acetylgalactosamine (GalNAc) is recognized by the asialoglycoprotein receptor (ASGPR) expressed on the surface of a hepatocyte for cellular uptake via endocytosis. Unlike natural phosphate, the 5′-VP on siRNA-GalNAc is not removed in endosome/lysosomes. The presence of 5′-VP on siRNA promotes RISC loading thereby improving the in vivo activity. On the other hand, the loss of 5′-P from siRNA-GalNAc hampers RISC loading. More information can be found in the communication by V. Jadhav et al. on page 985 in Issue 11, 2016 (DOI: 10.1002/cbic.201600130).