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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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  • 1RXi Pharmaceuticals Corporation, Gateway Life Sciences Park, Worcester, Massachusetts 01605, USA.

Abstract

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.

PMID:
21493786
[PubMed - indexed for MEDLINE]
PMCID:
PMC3096035
Free PMC Article
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