ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Functionally enhanced siRNA targeting TNFα attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
The trial behind it
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
11 citing papers in PubMed, 28 citations in OpenAlex.
- Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective.Pharmaceutics · 2022Review
- Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease.Pharmaceutics · 2020Review
- siRNA Targeting and Treatment of Gastrointestinal Diseases.Clinical and translational science · 2019Review
- Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.Cancer biology & therapy · 2016Article
- Nanomedicine and drug delivery strategies for treatment of inflammatory bowel disease.World journal of gastroenterology · 2015Review
- Dual TNF-α/IL-12p40 Interference as a Strategy to Protect Against Colitis Based on miR-16 Precursors With Macrophage Targeting Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Cyclooxygenase-2 silencing for the treatment of colitis: a combined in vivo strategy based on RNA interference and engineered Escherichia coli.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- The application of RNAi-based treatments for inflammatory bowel disease.Drug delivery and translational research · 2014Article
- Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF.EMBO molecular medicine · 2013Article
- RNA interference trigger variants: getting the most out of RNA for RNA interference-based therapeutics.Nucleic acid therapeutics · 2012Review
- Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering.Frontiers in genetics · 2012Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNFα) is a proinflammatory cytokine involved in the pathogenesis of inflammatory bowel disease (IBD). Although TNFα has been extensively targeted using systemic drugs, the use of antisense and small interfering RNA (siRNA) to drive down its expression at the site of inflammation should provide important advantages. In this study, native and chemically modified siRNA against TNFα was developed and characterized using a murine model of IBD. siRNA with 2'-O-methyl and propanediol modifications (siTNF-OMe-P) were resistant to nuclease degradation and provided better silencing efficacy in vitro as compared to unmodified siRNA. Every modification reduced nonspecific Toll-like receptor (TLR)-mediated immunomodulation in human peripheral blood mononuclear cells (PBMC) cells. Intrarectal administration of siTNF-OMe-P significantly ameliorated the clinical endpoints and histopathological severity in 5% dextran sulphate sodium (DSS)-treated mice as compared to unmodified and other chemically modified siRNAs. Differential gene expression assessed in siTNF-OMe-P-treated animals correlated with improved colon integrity and reduced TLR activation as compared to all treatment groups. All in all, this study demonstrates that propanediol and 2'-O-methyl modifications have profound functional consequences for siRNA efficacy in vivo. Consequently, this strategy has potential implications for therapeutic intervention in IBD and other diseases.
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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.