2′-hydroxyl modification improves enzymatic and thermal stability of mRNA

In a recent issue of Molecular Therapy Nucleic Acids, Yamada et al. reported that chemical modification of the 2′-hydroxyl groups of mRNA ribose improves enzymatic and thermal stability with reduced but still detectable translational activity.1 The 2′-hydroxyl groups are key contributors to mRNA degradation, both through ribonuclease (RNase) attack in physiological environments and hydrolysis during storage. Therefore, chemical modification of the 2′-hydroxyl groups is expected to mitigate both degradation mechanisms.