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.
Original language | English |
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Pages (from-to) | 1901-1908 |
Number of pages | 8 |
Journal | Biotechnology Letters |
Volume | 30 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2008 |
Keywords
- 2′-Ribose modification
- A-form helix
- Melting temperature
- RNA interference
- siRNA
- Stability