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Lack of interferon response in animals to naked siRNAs

Heidel, Jeremy D. and Hu, Siwen and Liu, Xian Fang and Triche, Timothy J. and Davis, Mark E. (2004) Lack of interferon response in animals to naked siRNAs. Nature Biotechnology, 22 (12). pp. 1579-1582. ISSN 1087-0156. doi:10.1038/nbt1038. https://resolver.caltech.edu/CaltechAUTHORS:20150513-095404544

[img] PDF (Supplementary Fig. 1 RNase digestion of poly(I:C) and siRNA) - Supplemental Material
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[img] PDF (Supplementary Fig. 2 Synthetic siRNA does not alter mouse CBC or liver enzyme levels) - Supplemental Material
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[img] PDF (Supplementary Fig. 3 Degradation kinetics of synthetic siRNA in mouse serum) - Supplemental Material
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[img] PDF (Supplementary Fig. 4 Sequence-specific target down-regulation by siRNA in RAW-264.7 cells) - Supplemental Material
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[img] PDF (Supplementary Fig. 5 Synthetic siRNA accomplishes sequence-specific RNAi of an exogenous target in mice) - Supplemental Material
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[img] PDF (Supplementary Fig. 6 Lack of IL-12 and IFN-a induction by siRNA in C57BL/6 mice) - Supplemental Material
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Abstract

RNA interference (RNAi) is rapidly becoming the method of choice for the elucidation of gene function and the identification of drug targets. As with other oligonucleotide-based strategies, RNAi is envisioned to ultimately be useful as a human therapeutic. Unlike previous nucleic acid therapeutics, small interfering RNAs have the potential to elicit immune responses via interactions with Toll-like receptor 3 and trigger interferon responses like long, double-stranded RNA and its analogs, such as poly(I:C). Recently, the safety of siRNAs has been questioned because they have been shown to trigger an interferon response in cultured cells. We show here that it is possible to administer naked, synthetic siRNAs to mice and downregulate an endogenous or exogenous target without inducing an interferon response.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nbt1038DOIArticle
http://www.nature.com/nbt/journal/v22/n12/full/nbt1038.htmlPublisherArticle
http://www.nature.com/nbt/journal/v22/n12/suppinfo/nbt1038_S1.htmlPublisherSupplementary Information
ORCID:
AuthorORCID
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2004 Macmillan Publishers Limited. Received 17 May; accepted 30 September 2004. The authors would like to thank Jean Lee and Hu Wong for critical blood chemistry and liver panel analyses. We thank Anton McCaffrey and Mark Kay for a donation of the plasmid used in our studies. J.D.H. acknowledges the Whitaker Foundation for a doctoral fellowship. S.H. is supported by an endowment in Molecular Pathology from the Las Madrinas Foundation at CHLA.
Funders:
Funding AgencyGrant Number
Whitaker FoundationUNSPECIFIED
Las Madrinas FoundationUNSPECIFIED
Issue or Number:12
DOI:10.1038/nbt1038
Record Number:CaltechAUTHORS:20150513-095404544
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150513-095404544
Official Citation:Heidel, J. D., Hu, S., Liu, X. F., Triche, T. J., & Davis, M. E. (2004). Lack of interferon response in animals to naked siRNAs. [10.1038/nbt1038]. Nat Biotech, 22(12), 1579-1582.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57485
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:13 May 2015 19:04
Last Modified:10 Nov 2021 21:50

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