title: Potent and systematic RNAi mediated silencing with single oligonucleotide compounds.
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.
authors.affiliation: RXi Pharmaceuticals Corporation, Gateway Life Sciences Park, Worcester, Massachusetts 01605, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lapierre
authors.forename: William
authors.initials: W
authors.lastname: Salomon
authors.forename: James
authors.initials: J
authors.lastname: Cardia
authors.forename: Karen
authors.initials: K
authors.lastname: Bulock
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Lam
authors.forename: William J
authors.initials: WJ
authors.lastname: Stanney
authors.forename: Glenna
authors.initials: G
authors.lastname: Ford
authors.forename: Bernice
authors.initials: B
authors.lastname: Smith-Anzures
authors.forename: Tod
authors.initials: T
authors.lastname: Woolf
authors.forename: Joanne
authors.initials: J
authors.lastname: Kamens
authors.forename: Anastasia
authors.initials: A
authors.lastname: Khvorova
authors.forename: Dmitry
authors.initials: D
authors.lastname: Samarsky
mesh_terms: D002478:Cells, Cultured; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D012313:RNA