Role of a “Magic” Methyl: 2′-Deoxy-2′-α-F-2′-β-<i>C</i>-methyl Pyrimidine Nucleotides Modulate RNA Interference Activity through Synergy with 5′-Phosphate Mimics and Mitigation of Off-Target Effects
Dale C. Guenther, S. Mori, Shigeo Matsuda, Jason A. Gilbert, Jennifer L. S. Willoughby, Sarah Hyde, Anna Bisbe, Yongfeng Jiang, Saket Agarwal, Mimouna Madaoui, Maja M. Janas, Klaus Charissé, Martin A. Maier, Martin Egli, Muthiah Manoharan
Abstract
-methyl-containing sugar ring. These data indicate that 2'-F/Me nucleotides are promising tools for nucleic acid-based therapeutic applications to increase potency, duration, and safety.
Topics & Concepts
ChemistryOligonucleotideSteric effectsNucleotideStereochemistryRNASmall interfering RNANucleosideGene silencingOligonucleotide synthesisDuplex (building)Nucleic acidDNABiochemistryGeneRNA Interference and Gene DeliveryAdvanced biosensing and bioanalysis techniquesRNA modifications and cancer