ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Engineered Circular RNA Sponges Act as miRNA Inhibitors to Attenuate Pressure Overload-Induced Cardiac Hypertrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed.
- Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.European heart journal · 2021Trial
- Emerging strategies and innovations in circular RNA synthesis.Molecular therapy. Nucleic acids · 2026Review
- The emerging roles of small nucleolar RNAs, piwi-interacting RNAs, tRNA-derived small RNAs, and circular RNAs in the regulation of cardiac hypertrophy, ischemic heart disease, and heart failure.Genes & diseases · 2026Review
- Direct Cytosolic Delivery of Amphiphilic Framework Nucleic Acids for RNA Interference.Angewandte Chemie (International ed. in English) · 2026Article
- Engineering circular RNA expression systems to minimize contaminating linear RNA byproducts.bioRxiv : the preprint server for biology · 2026Article
- The cardiac protective human circular RNA circKLHL20_009 sponges miR-31-5p to ameliorate myocardial hypertrophy and fibrosis through suppressing β-catenin signaling.Acta pharmacologica Sinica · 2026Article
- CircRNA-regulated programmed cell death networks in cardiomyocytes: Molecular crosstalk and therapeutic translation.Non-coding RNA research · 2026Review
- Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation.Precision clinical medicine · 2026Review
- Site-Specifically Modified Circular Ribonucleic Acid Serves as Multitarget miRNA Sponge with Low Immunogenicity.Journal of the American Chemical Society · 2026Article
- circ_0103896/miR-432-5p/FTO feedback loop suppresses the formation and progression of intracranial aneurysm.Non-coding RNA research · 2026Article
- CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system.Biochemistry and biophysics reports · 2026Review
- Therapeutic rewiring of ceRNA networks: a computational pipeline for drug repurposing in acute kidney injury via circRNA-miRNA-mRNA axis disruption.Human genomics · 2026Review
- SUPER: Upcycling Genetic Parts for Precise Gene Expression Control, Leakage Minimization, and Genetic Circuit Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circular RNAs as Biomarkers and Therapeutic Targets in Diabetic Cardiovascular Complications.Endocrinology, diabetes & metabolism · 2026Review
- Noncoding RNA in Clinical Trials: Diagnostic and Therapeutical Prospects.Experientia supplementum (2012) · 2026Review
- circSP199a, a circularized RNA sponge targeting miR-199a-5p and -3p, mitigates mouse cardiac hypertrophy and fibrosis.Acta pharmacologica Sinica · 2026Article
- Molecular basis of backsplicing regulation and its application to manipulate circRNA levels.RNA biology · 2025Review
- Circular RNA: From non-coding regulators to functional protein encoders.Pharmaceutical science advances · 2025Review
- Antisense molecules: A promising new therapy for atopic dermatitis.Acta pharmaceutica Sinica. B · 2025Review
- Using modified mRNA for cardiomyocyte proliferation and cardiac genetic disease modelling and treatment.Biochemical Society transactions · 2025Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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