Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ymthe.2020.04.006
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dc.titleEngineered Circular RNA Sponges Act as miRNA Inhibitors to Attenuate Pressure Overload-Induced Cardiac Hypertrophy
dc.contributor.authorLavenniah, Annadoray
dc.contributor.authorTuan, Danh Anh Luu
dc.contributor.authorLi, Yiqing Peter
dc.contributor.authorLim, Tingsen Benson
dc.contributor.authorJiang, Jianming
dc.contributor.authorAckers-Johnson, Matthew
dc.contributor.authorFoo, Roger
dc.date.accessioned2020-07-24T03:01:28Z
dc.date.available2020-07-24T03:01:28Z
dc.date.issued2020-06-03
dc.identifier.citationLavenniah, Annadoray, Tuan, Danh Anh Luu, Li, Yiqing Peter, Lim, Tingsen Benson, Jiang, Jianming, Ackers-Johnson, Matthew, Foo, Roger (2020-06-03). Engineered Circular RNA Sponges Act as miRNA Inhibitors to Attenuate Pressure Overload-Induced Cardiac Hypertrophy. MOLECULAR THERAPY 28 (6) : 1506-1517. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ymthe.2020.04.006
dc.identifier.issn1525-0016
dc.identifier.issn1525-0024
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/171691
dc.description.abstract© 2020 The Author(s) Circular RNAs (circRNAs) sequester microRNAs (miRNAs) and repress their endogenous activity. We hypothesized that artificial circRNA sponges (circmiRs) can be constructed to target miRNAs therapeutically, with a low dosage requirement and extended half-lives compared to current alternatives. This could present a new treatment approach for critical global pathologies, including cardiovascular disease. Here, we constructed a circmiR sponge to target known cardiac pro-hypertrophic miR-132 and -212. Expressed circmiRs competitively inhibited miR-132 and -212 activity in luciferase rescue assays and showed greater stability than linear sponges. A design containing 12 bulged binding sites with 12 nucleotides spacing was determined to be optimal. Adeno-associated viruses (AAVs) were used to deliver circmiRs to cardiomyocytes in vivo in a transverse aortic constriction (TAC) mouse model of cardiac disease. Hypertrophic disease characteristics were attenuated, and cardiac function was preserved in treated mice, demonstrating the potential of circmiRs as novel therapeutic tools. Subsequently, group I permutated intron-exon sequences were used to directly synthesize exogenous circmiRs, which showed greater in vitro efficacy than the current gold standard antagomiRs in inhibiting miRNA function. Engineered circRNAs thus offer exciting potential as future therapeutics.
dc.language.isoen
dc.publisherCELL PRESS
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiotechnology & Applied Microbiology
dc.subjectGenetics & Heredity
dc.subjectMedicine, Research & Experimental
dc.subjectResearch & Experimental Medicine
dc.subjectMICRORNA SPONGES
dc.subjectIN-VIVO
dc.subjectBIOGENESIS
dc.subjectEXPRESSION
dc.subjectPREDICTION
dc.subjectINTRON
dc.subjectHEART
dc.subjectAAV
dc.typeArticle
dc.date.updated2020-07-23T08:10:07Z
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1016/j.ymthe.2020.04.006
dc.description.sourcetitleMOLECULAR THERAPY
dc.description.volume28
dc.description.issue6
dc.description.page1506-1517
dc.published.statePublished
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