Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy.
Identifieur interne : 002E74 ( Main/Curation ); précédent : 002E73; suivant : 002E75Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy.
Auteurs : Dong-Ho Kim ; Mark A. Behlke ; Scott D. Rose ; Mi-Sook Chang ; Sangdun Choi ; John J. RossiSource :
- Nature biotechnology [ 1087-0156 ] ; 2005.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Petit ARN interférent, Régulation de l'expression des gènes.
- métabolisme : Ribonuclease III.
- physiologie : Extinction de l'expression des gènes.
- Ciblage de gène, Génie génétique, Petit ARN interférent, Ribonuclease III, Transfection.
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : RNA, Small Interfering, Ribonuclease III.
- genetics : Gene Expression Regulation, RNA, Small Interfering.
- chemical , metabolism : Ribonuclease III.
- methods : Gene Targeting, Genetic Engineering, Transfection.
- physiology : Gene Silencing.
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.
DOI: 10.1038/nbt1051
PubMed: 15619617
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pubmed:15619617Le document en format XML
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<term>Genetic Engineering (methods)</term>
<term>RNA, Small Interfering (chemistry)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>Ribonuclease III (chemistry)</term>
<term>Ribonuclease III (metabolism)</term>
<term>Transfection (methods)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Ciblage de gène ()</term>
<term>Extinction de l'expression des gènes (physiologie)</term>
<term>Génie génétique ()</term>
<term>Petit ARN interférent ()</term>
<term>Petit ARN interférent (génétique)</term>
<term>Ribonuclease III ()</term>
<term>Ribonuclease III (métabolisme)</term>
<term>Régulation de l'expression des gènes (génétique)</term>
<term>Transfection ()</term>
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<term>Ribonuclease III</term>
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<term>RNA, Small Interfering</term>
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<term>Transfection</term>
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<term>Petit ARN interférent</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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