Improved serum stability and biophysical properties of siRNAs following chemical modifications
Ik Sang Cho1, Jung Kim, Do Hwan Lim
1Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea.
Abstract:
Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2'-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2'-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.
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