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pubmed-article:19144911pubmed:abstractTextsiRNAs mediate sequence-specific gene silencing in cultured mammalian cells but also silence unintended transcripts. Many siRNA off-target transcripts match the guide-strand "seed region," similar to the way microRNAs match their target sites. The extent to which this seed-matched, microRNA-like, off-target silencing affects the specificity of therapeutic siRNAs in vivo is currently unknown. Here, we compare microRNA-like off-target regulations in mouse liver in vivo with those seen in cell culture for a series of therapeutic candidate siRNAs targeting Apolipoprotein B (APOB). Each siRNA triggered regulation of consistent microRNA-like off-target transcripts in mouse livers and in cultured mouse liver tumor cells. In contrast, there was only random overlap between microRNA-like off-target transcripts from cultured human and mouse liver tumor cells. Therefore, siRNA therapeutics may trigger microRNA-like silencing of many unintended targets in vivo, and the potential toxicities caused by these off-target gene regulations cannot be accurately assessed in rodent models.lld:pubmed
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pubmed-article:19144911pubmed:authorpubmed-author:DaiHongyueHlld:pubmed
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pubmed-article:19144911pubmed:authorpubmed-author:BartzSteven...lld:pubmed
pubmed-article:19144911pubmed:authorpubmed-author:SachsAlan BABlld:pubmed
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pubmed-article:19144911pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:19144911pubmed:year2009lld:pubmed
pubmed-article:19144911pubmed:articleTitleMicroRNA-like off-target transcript regulation by siRNAs is species specific.lld:pubmed
pubmed-article:19144911pubmed:affiliationRosetta Inpharmatics LLC, Seattle, Washington 98109, USA.lld:pubmed
pubmed-article:19144911pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19144911pubmed:publicationTypeComparative Studylld:pubmed
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