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Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy

Kim, Dong-Ho and Behlke, Mark A. and Rose, Scott D. and Chang, Mi-Sook and Choi, Sangdun and Rossi, John J. (2005) Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nature Biotechnology, 23 (2). pp. 222-226. ISSN 1087-0156. https://resolver.caltech.edu/CaltechAUTHORS:20150401-144628864

[img] PDF (Supplementary Fig. 1) - Supplemental Material
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[img] PDF (Supplementary Fig. 2 ESI mass spectra of the 27mer duplex EGFPS1 27+0 before (top) and after (bottom) incubation with Dicer are shown) - Supplemental Material
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[img] PDF (Supplementary Fig. 3 Sequence specificity of Dicer substrate 27mer dsRNAs) - Supplemental Material
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[img] PDF (Supplementary Fig. 4 SiRNAs and Dicer substrate dsRNAs do not induce interferons or activate PKR or generate specific "off target effects") - Supplemental Material
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[img] PDF (Supplementary Table 1 Summary of oligonucleotide reagents) - Supplemental Material
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[img] PDF (Supplementary Table 2 Molecular weights of possible 21mer duplexes derived from the 27mer duplex by Dicer processing) - Supplemental Material
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Abstract

RNA interference (RNAi) is the process of sequence-specific post-transcriptional gene silencing triggered by double-stranded RNAs. In attempts to identify RNAi triggers that effectively function at lower concentrations, we found that synthetic RNA duplexes 25–30 nucleotides in length can be up to 100-fold more potent than corresponding conventional 21-mer small interfering RNAs (siRNAs). Some sites that are refractory to silencing by 21-mer siRNAs can be effectively targeted by 27-mer duplexes, with silencing lasting up to 10 d. Notably, the 27-mers do not induce interferon or activate protein kinase R (PKR). The enhanced potency of the longer duplexes is attributed to the fact that they are substrates of the Dicer endonuclease, directly linking the production of siRNAs to incorporation in the RNA-induced silencing complex. These results provide an alternative strategy for eliciting RNAi-mediated target cleavage using low concentrations of synthetic RNA as substrates for cellular Dicer-mediated cleavage.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nbt1051DOIArticle
http://www.nature.com/nbt/journal/v23/n2/full/nbt1051.htmlPublisherArticle
http://rdcu.be/csfpPublisherFree ReadCube access
http://www.nature.com/nbt/journal/v23/n2/suppinfo/nbt1051_S1.htmlPublisherSupplementary Information
Additional Information:© 2005 Nature Publishing Group. Received 22 July; accepted 1 November 2004; Published online 26 December 2004. D.K. is a Beckman Fellow. This work was supported by a grant from the Arnold and Mabel Beckman Foundation and the US National Institutes of Health (AI29329 and AI42552, and HL074704 to J.J.R.). The authors wish to dedicate this work to the memory of Arnold Beckman, who recently passed away.
Funders:
Funding AgencyGrant Number
Arnold and Mabel Beckman FoundationUNSPECIFIED
NIHAI29329
NIHAI42552
NIHHL074704
Issue or Number:2
Record Number:CaltechAUTHORS:20150401-144628864
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150401-144628864
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56299
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Apr 2015 22:00
Last Modified:03 Oct 2019 08:12

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