Immune activation by siRNA/liposome complexes in mice is sequence- independent: lack of a role for toll-like receptor 3 signaling

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dc.contributor.authorJ Y Kim-
dc.contributor.authorS Choung-
dc.contributor.authorE J Lee-
dc.contributor.authorYoung Joo Kim-
dc.contributor.authorY C Choi-
dc.date.accessioned2017-04-19T09:08:21Z-
dc.date.available2017-04-19T09:08:21Z-
dc.date.issued2007-
dc.identifier.issn1016-8478-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8135-
dc.description.abstractImprovement 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.-
dc.publisherKorea Soc-Assoc-Inst-
dc.titleImmune activation by siRNA/liposome complexes in mice is sequence- independent: lack of a role for toll-like receptor 3 signaling-
dc.title.alternativeImmune activation by siRNA/liposome complexes in mice is sequence- independent: lack of a role for toll-like receptor 3 signaling-
dc.typeArticle-
dc.citation.titleMolecules and Cells-
dc.citation.number2-
dc.citation.endPage254-
dc.citation.startPage247-
dc.citation.volume24-
dc.contributor.affiliatedAuthorYoung Joo Kim-
dc.contributor.alternativeName김지영-
dc.contributor.alternativeName정소림-
dc.contributor.alternativeName이은주-
dc.contributor.alternativeName김영주-
dc.contributor.alternativeName최영철-
dc.identifier.bibliographicCitationMolecules and Cells, vol. 24, no. 2, pp. 247-254-
dc.subject.keywordchemical modification-
dc.subject.keywordimmune activation-
dc.subject.keywordsiRNA-
dc.subject.keywordtoll-like receptor 3-
dc.subject.localChemical modification-
dc.subject.localchemical modification-
dc.subject.localimmune activation-
dc.subject.localsiRNA-
dc.subject.localSiRNA-
dc.subject.localToll-like receptor 3 (TLR3)-
dc.subject.localtoll-like receptor 3-
dc.description.journalClassY-
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