ArticleNucleic acids research2012
Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 8 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Chemical modification patterns for microRNA therapeutic mimics: a structure-activity relationship (SAR) case-study on miR-200c.Nucleic acids research · 2024Article
- Non-viral gene therapy using RNA interference with PDGFR-α mediated epithelial-mesenchymal transformation for proliferative vitreoretinopathy.Materials today. Bio · 2023Article
- Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein.Pharmaceutical biology · 2022Article
- Effective tools for RNA-derived therapeutics: siRNA interference or miRNA mimicry.Theranostics · 2021Review
- MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing.Nanomaterials (Basel, Switzerland) · 2019Article
- Blocking sense-strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA.EMBO molecular medicine · 2016Article
- c-Met targeting enhances the effect of irradiation and chemical agents against malignant colon cells harboring a KRAS mutation.PloS one · 2014Article
- RNAi2013: RNAi at Oxford.Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research · 2013Article
Corrections and comments
- Expression of concern
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Strategies to regulate gene function frequently use small interfering RNAs (siRNAs) that can be made from their shRNA precursors via Dicer. However, when the duplex components of these siRNA effectors are expressed from their respective coding genes, the RNA interference (RNAi) activity is much reduced. Here, we explored the mechanisms of action of shRNA and siRNA and found the expressed siRNA, in contrast to short hairpin RNA (shRNA), exhibits strong strand antagonism, with the sense RNA negatively and unexpectedly regulating RNAi. Therefore, we altered the relative levels of strands of siRNA duplexes during their expression, increasing the level of the antisense component, reducing the level of the sense component, or both and, in this way we were able to enhance the potency of the siRNA. Such vector-delivered siRNA attacked its target effectively. These findings provide new insight into RNAi and, in particular, they demonstrate that strand antagonism is responsible for making siRNA far less potent than shRNA.
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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 OpenQuestion graph.