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

doi:10.1038/nmeth.1903

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^*

^*此作品的通信作者

數據科學與工程研究所

研究成果: Article › 同行評審

181 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
卷	9
發行號	4
DOIs	https://doi.org/10.1038/nmeth.1903
出版狀態	Published - 4月 2012

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

abstract = "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.",

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

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AU - Xie, Jun

AU - Ameres, Stefan L.

AU - Friedline, Randall

AU - Hung, Jui-Hung

AU - Zhang, Yu

AU - Xie, Qing

AU - Zhong, Li

AU - Su, Qin

AU - He, Ran

AU - Li, Mengxin

AU - Li, Huapeng

AU - Mu, Xin

AU - Zhang, Hongwei

AU - Broderick, Jennifer A.

AU - Kim, Jason K.

AU - Weng, Zhiping

AU - Flotte, Terence R.

AU - Zamore, Phillip D.

AU - Gao, Guangping

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

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