Tissue-specific gene silencing monitored in circulating RNA

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 quantita...

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Bibliographic Details
Published in:RNA (Cambridge) 2014-02, Vol.20 (2), p.143-149
Main Authors: Sehgal, Alfica, Chen, Qingmin, Gibbings, Derrick, Sah, Dinah W Y, Bumcrot, David
Format: Article
Language:English
Subjects:
Aged
alpha-Fetoproteins - genetics
Animals
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Gene Expression
Gene Knockdown Techniques
Glypicans - genetics
Humans
Liver - metabolism
Macaca fascicularis
Male
Organ Specificity
Rats
Rats, Sprague-Dawley
RNA Interference
RNA, Messenger - blood
RNA, Messenger - genetics
RNA, Small Interfering - genetics
Species Specificity
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Summary: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.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.042507.113