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RNA. 2011 Jun;17(6):1032-7. doi: 10.1261/rna.2399411. Epub 2011 Apr 14.

Potent and systematic RNAi mediated silencing with single oligonucleotide compounds.

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RXi Pharmaceuticals Corporation, Gateway Life Sciences Park, Worcester, Massachusetts 01605, USA.


RNA interference (RNAi) has been established as an important tool for functional genomics studies and has great promise as a therapeutic intervention for human diseases. In mammalian cells, RNAi is conventionally induced by 19-27-bp RNA duplexes generated by hybridization of two complementary oligonucleotide strands (oligos). Here we describe a novel class of RNAi molecules composed of a single 25-28-nucleotide (nt) oligo. The oligo has a 16-nt mRNA targeting region, followed by an additional 8-10 nt to enable self-dimerization into a partially complementary duplex. Analysis of numerous diverse structures demonstrates that molecules composed of two short helices separated by a loop can efficiently enter and activate the RNA-induced silencing complex (RISC). This finding enables the design of highly effective single-oligo compounds for any mRNA target.

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