ArticleMolecular therapy. Nucleic acids2019
Nucleotide Modification Alters MicroRNA-Dependent Silencing of MicroRNA Switches.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
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- mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.Nature biotechnology · 2026Article
- MicroRNA chemical modifications in post-transcriptional gene silencing and human diseases.Molecular therapy. Nucleic acids · 2025Review
- Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level.Nature biomedical engineering · 2025Review
- The Life of MicroRNAs: Biogenesis, Function and Decay in Cancer.Biomolecules · 2025Review
- MicroRNAs won the Nobel Prize. Now, can extracellular vesicles help them become drugs?Extracellular vesicle · 2025Article
- Significance of miR-1290 in glioblastoma patients with epilepsy.Scientific reports · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Deconvolution of synthetic mRNA expression: Nucleoside chemistry alters translatability.Bioengineering & translational medicine · 2024Article
- Global RNA modifications to the MALAT1 triple helix differentially affect thermostability and weaken binding to METTL16.The Journal of biological chemistry · 2024Article
- SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas.Cell host & microbe · 2023Article
- Synthetic circular RNA switches and circuits that control protein expression in mammalian cells.Nucleic acids research · 2023Article
- Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Aptamer-Array-Guided Protein Assembly Enhances Synthetic mRNA Switch Performance.Angewandte Chemie (International ed. in English) · 2022Article
- Nanotechnology for cardiovascular diseases.Innovation (Cambridge (Mass.)) · 2022Review
- Structure Characterization ofFrontiers in microbiology · 2022Article
- Therapeutic Significance of microRNA-Mediated Regulation of PARP-1 in SARS-CoV-2 Infection.Non-coding RNA · 2021Article
- Pseudouridines in RNAs: switching atoms means shifting paradigms.FEBS letters · 2021Review
- Self-assembled miRNA-switch nanoparticles target denuded regions and prevent restenosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
mRNA therapeutics hold great promise for the treatment of human diseases. While incorporating naturally occurring modified nucleotides during synthesis has greatly increased their potency and safety, challenges in selective expression have hindered clinical applications. MicroRNA (miRNA)-regulated in vitro-transcribed mRNAs, called miRNA switches, have been used to control the expression of exogenous mRNA in a cell-selective manner. However, the effect of nucleotide modifications on miRNA-dependent silencing has not been examined. Here we show that the incorporation of pseudouridine, N1-methylpseudourdine, or pseudouridine and 5-methylcytidine, which increases translation, tends to decrease the regulation of miRNA switches. Moreover, pseudouridine and 5-methylcytidine modification enables one miRNA target site at the 3' UTR to be as effective as four target sites. We also demonstrate that the effects of pseudouridine, pseudouridine and 5-methylcytidine, and N1-methylpseudourdine modification are miRNA switch specific and do not correlate with the proportion of modified nucleotides in the miRNA target site. Furthermore, modified miRNA switches containing seed-complementary target sites are poorly regulated by miRNA. We also show that placing the miRNA target site in the 5' UTR of the miRNA switch abolishes the effect of nucleotide modification on miRNA-dependent silencing. This work provides insights into the influence of nucleotide modifications on miRNA-dependent silencing and informs the design of optimal miRNA switches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.