Structural basis for the synergy of 4′- and 2′-modifications on siRNA nuclease resistance, thermal stability and RNAi activity

• Published in: Nucleic acids research Vol. 46; no. 16; pp. 8090 - 8104
• Main Authors: Harp, Joel M, Guenther, Dale C, Bisbe, Anna, Perkins, Lydia, Matsuda, Shigeo, Bommineni, Gopal R, Zlatev, Ivan, Foster, Donald J, Taneja, Nate, Charisse, Klaus, Maier, Martin A, Rajeev, Kallanthottathil G, Manoharan, Muthiah, Egli, Martin
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 19.09.2018
• Subjects: Chemical Biology and Nucleic Acid Chemistry; Humans; Models, Molecular; Nucleic Acid Conformation; Oligonucleotides - chemistry; Oligonucleotides - genetics; Phosphates - chemistry; Ribonucleases - chemistry; Ribose - chemistry; RNA Interference; RNA Stability - genetics; RNA, Small Interfering - chemistry; Thermodynamics; Uridine - chemistry; Uridine - genetics

Abstract Chemical modification is a prerequisite of oligonucleotide therapeutics for improved metabolic stability, uptake and activity, irrespective of their mode of action, i.e. antisense, RNAi or aptamer. Phosphate moiety and ribose C2′/O2′ atoms are the most common sites for modification. Compare...