상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

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

Authors 

J Y KimS ChoungE J LeeYoung Joo KimY C Choi

Publisher 

Springer Verlag (Germany)

Issue Date 

2007

Citation 

Molecules and Cells, vol. 24, no. 2, pp. 247-254

Keywords 

chemical modificationimmune activationsiRNAtoll-like receptor 31,2 dioleoyl 3 trimethylammoniopropanealpha interferonliposomephosphorothioic acidsmall interfering RNAanimal experiment

Abstract 

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.

ISSN 

1016-8478

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)