Phosphorothioate stereochemistry in therapeutic oligonucleotides

The idea that the stereochemistry of the phosphorothioate backbone modifications may influence the pharmacological properties of therapeutic oligonucleotides is not a new concept but has regained attention due to improvements in the synthesis of stereo-selective oligonucleotides1. Several recent papers have investigated this idea in antisense2, immunomodulatory3 and splice-switching oligonucleotides4 as well as siRNAs5. In general,…