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dc.contributor.authorXie, Jun
dc.contributor.authorAmeres, Stefan L.
dc.contributor.authorFriedline, Randall H.
dc.contributor.authorHung, Jui-Hung
dc.contributor.authorZhang, Yu
dc.contributor.authorXie, Qing
dc.contributor.authorZhong, Li
dc.contributor.authorSu, Qin
dc.contributor.authorHe, Ran
dc.contributor.authorLi, Mengxin
dc.contributor.authorLi, Huapeng
dc.contributor.authorMu, Xin
dc.contributor.authorZhang, Hongwei
dc.contributor.authorBroderick, Jennifer A
dc.contributor.authorKim, Jason K.
dc.contributor.authorWeng, Zhiping
dc.contributor.authorFlotte, Terence R.
dc.contributor.authorZamore, Phillip D.
dc.contributor.authorGao, Guangping
dc.date2022-08-11T08:10:14.000
dc.date.accessioned2022-08-23T17:00:44Z
dc.date.available2022-08-23T17:00:44Z
dc.date.issued2012-03-04
dc.date.submitted2012-04-30
dc.identifier.citation<p>Nat Methods. 2012 Mar 4;9(4):403-9. doi: 10.1038/nmeth.1903. <a href="http://dx.doi.org/10.1038/nmeth.1903" target="_blank">Link to article on publisher's site</a></p>
dc.identifier.issn1548-7105
dc.identifier.doi10.1038/nmeth.1903
dc.identifier.pmid22388288
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43857
dc.description<p>Co-author Jennifer A. Broderick is a student in the Neuroscience program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.</p>
dc.description.abstractUnderstanding 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.
dc.language.isoen_US
dc.publisherNature Pub. Group
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22388288&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420816/
dc.subjectDependovirus
dc.subjectGenetic Vectors
dc.subjectMicroRNAs
dc.subjectDyslipidemias
dc.subjectUMCCTS funding
dc.subjectAllergy and Immunology
dc.subjectNutritional and Metabolic Diseases
dc.subjectPediatrics
dc.subjectRespiratory Tract Diseases
dc.titleLong-term, efficient inhibition of microRNA function in mice using rAAV vectors
dc.typeJournal Article
dc.source.journaltitleNature methods
dc.source.volume9
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_pulmonary/69
dc.identifier.contextkey2810694
html.description.abstract<p>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.</p>
dc.identifier.submissionpathpeds_pulmonary/69
dc.contributor.departmentDepartment of Pediatrics
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentMouse Phenotyping Center
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentDepartment of Microbiology and Physiology Systems
dc.contributor.departmentGene Therapy Center
dc.source.pages403-9


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