Expanding the binding space of argonaute-2: incorporation of either E or Z isomers of 6′-vinylphosphonate at the 5′ end of the antisense strand improves RNAi activity

Abstract

A phosphate or a phosphate mimic at the 5′ terminus of the antisense strand of a small interfering RNA (siRNA) is required for efficient loading into the RISC complex through the MID domain binding pocket of Ago2. Introduction of 5′-E-vinylphosphonate improves this binding and siRNA potency, but the Z isomer does not. Here, we demonstrate that both the E and Z isomers of 6′-vinylphosphonate at the 5′ ends of antisense strands of siRNAs have equivalent potencies.