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Synthetic dsRNA Dicer Substrates Enhance RNAi Potency and Efficacy
Behlke, Mark A.
Rose, Scott D.
Rossi, John J.
Article from Journal - ilmiah internasional
Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 2 (Feb. 2005)
potency and efficacy
Perpustakaan Pusat (Semanggi)
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Lihat Detail Induk
RNA interference (RNAi) is the process of sequence specific post transcriptional gene silencing triggered by double stranded RNAs. In attempts to identity 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 interdering 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 elicting RNAi mediated target cleavage using low concentrations of synthetic RNA as substarted for cellular Dicer mediated cleavage.
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