Improved serum stability and biophysical properties of siRNAs following chemical modifications |
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Authors: | Ik Sang Cho Jung Kim Do Hwan Lim Hee-Chul Ahn Hyunggee Kim Kang-Bong Lee Young Sik Lee |
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Institution: | (1) Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea;(2) Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, 136-791, South Korea |
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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.
Ik Sang Cho and Jung Kim contributed equally to this work. |
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Keywords: | A-form helix Melting temperature 2′ -Ribose modification RNA interference siRNA Stability |
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