A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects
J.B. Bramsen, M.M. Pakula, T.B. Hansen, C. Bus, N. Langkjær, D. Odadzic, R. Smicius, S.L. Wengel, J. Chattopadhyaya, J.W. Engels, P. Herdewijn, J. Wengel and J. Kjems, Nucleic Acids Research, 38, 5761-5773, 2010.
The authors have found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA-target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low.