title: Tissue-specific gene silencing monitored in circulating RNA.
abstract: Pharmacologic target gene modulation is the primary objective for RNA antagonist strategies and gene therapy. Here we show that mRNAs encoding tissue-specific gene transcripts can be detected in biological fluids and that RNAi-mediated target gene silencing in the liver and brain results in quantitative reductions in serum and cerebrospinal fluid mRNA levels, respectively. Further, administration of an anti-miRNA oligonucleotide resulted in decreased levels of the miRNA in circulation. Moreover, ectopic expression of an adenoviral transgene in the liver was quantified based on measurement of serum mRNA levels. This noninvasive method for monitoring tissue-specific RNA modulation could greatly advance the clinical development of RNA-based therapeutics.
authors.forename: Alfica
authors.initials: A
authors.lastname: Sehgal
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Chen
authors.forename: Derrick
authors.initials: D
authors.lastname: Gibbings
authors.forename: Dinah W Y
authors.initials: DW
authors.lastname: Sah
authors.forename: David
authors.initials: D
authors.lastname: Bumcrot
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D053673:Glypicans / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009928:Organ Specificity; D034622:RNA Interference; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000509:alpha-Fetoproteins
keywords: RNAi; circulating RNA; exosome; gene silencing; in vivo delivery