Synthesis, physicochemical and biological properties of oligonucleotides incorporated with amino-isonucleosides

Antisense oligonucleotides (ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression, and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy. In order to improve bioactivity properties and physicochemical properties of siRNA, we synthesized a novel class of ASONs II–VII incorporated with amino-isonucleoside (isoA (1) and isoA (2)) for investigation on basic physicochemical properties. Then we designed amino-isonucleoside (isoA (1), isoA (2) and isoT (1)) incorporated siRNA 2–7. Some meaningful results have been obtained from the physicochemical property experiments in ASONs. In RNAi potency experiments, we investigated RNAi potency of each strand of the siRNA. These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity. Reduced off target effect from sense strand loading in siRNA application was observed.