Immune activation by siRNA/liposome complexes in mice is sequence- independent: lack of a role for toll-like receptor 3 signaling
Cited 0 time in
- Immune activation by siRNA/liposome complexes in mice is sequence- independent: lack of a role for toll-like receptor 3 signaling
- J Y Kim; S Choung; E J Lee; Young Joo Kim; Y C Choi
- Bibliographic Citation
- Molecules and Cells, vol. 24, no. 2, pp. 247-254
- Publication Year
- Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon α, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2′-OMe, 2′-F, and phosphorothioate substitutions, introduction of as little as three 2′-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.
- chemical modificationsiRNAtoll-like receptor 3immune activation
- Korea Soc-Assoc-Inst
- Appears in Collections:
- 1. Journal Articles > Journal Articles
- Files in This Item:
Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.