Long-term, efficient inhibition of microRNA function in mice using rAAV vectors

Jun Xie, Stefan L. Ameres, Randall Friedline, Jui-Hung Hung, Yu Zhang, Qing Xie, Li Zhong, Qin Su, Ran He, Mengxin Li, Huapeng Li, Xin Mu, Hongwei Zhang, Jennifer A. Broderick, Jason K. Kim, Zhiping Weng, Terence R. Flotte, Phillip D. Zamore, Guangping Gao*

*Corresponding author for this work

研究成果: Article同行評審

138 引文 斯高帕斯(Scopus)

摘要

Understanding the function of individual microRNA (miRNA) species in mice would require the production of hundreds of loss-of-function strains. To accelerate analysis of miRNA biology in mammals, we combined recombinant adeno-associated virus (rAAV) vectors with miRNA 'tough decoys' (TuDs) to inhibit specific miRNAs. Intravenous injection of rAAV9 expressing anti-miR-122 or anti-let-7 TuDs depleted the corresponding miRNA and increased its mRNA targets. rAAV producing anti-miR-122 TuD but not anti-let-7 TuD reduced serum cholesterol by >30% for 25 weeks in wild-type mice. High-throughput sequencing of liver miRNAs from the treated mice confirmed that the targeted miRNAs were depleted and revealed that TuDs induced miRNA tailing and trimming in vivo. rAAV-mediated miRNA inhibition thus provides a simple way to study miRNA function in adult mammals and a potential therapy for dyslipidemia and other diseases caused by miRNA deregulation.

原文English
頁(從 - 到)403-409
頁數7
期刊Nature Methods
9
發行號4
DOIs
出版狀態Published - 1 四月 2012

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