The MOE Modification of RNA: Origins and Widescale Impact on the Oligonucleotide Therapeutics Field

In an article published by Helvetica Chimica Acta in 1995, chemist P. Martin describes the synthesis of 2?-O-alkylated ribonucleosides for use therapeutic antisense oligonucleotides (ASOs). This work was motivated need a modified ribose structure that compatible with solid-phase protocols and that, when incorporated into oligonucleotide, would render it resistant to nucleases without attenuating its ability hybridize complementary RNA target. described robust route 2?-O-alkylribonucleosides which 2?-OH group is substituted 2?-ethylene glycol derivatives. Oligonucleotides containing these modifications displayed überraschende Eigenschaften – ‘surprising properties’ notably, higher affinity specificity substrates greater stability relative their unmodified counterparts. Today, modification universally known field as 2?-O-methoxyethyl (MOE) modification. The chemistry features four ASO drugs many others clinical trials. Here, we 1) summarize MOE-modified ribose; 2) outline properties reported Martin’s article; 3) highlight first approved drugs, mipomersen nusinersen; 4) survey ASOs development. outlook, put developments context consider future possibilities MOE