ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
An endogenous TNF-alpha antagonist induced by splice-switching oligonucleotides reduces inflammation in hepatitis and arthritis mouse models.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.Frontiers in neuroscience · 2022Pooled it
- Effect of chemical modification on the exon-skipping activity of heteroduplex oligonucleotides.Molecular therapy. Nucleic acids · 2025Article
- Risk Allele rs117026326-Mediated Alternative Splicing of GTF2I Promotes B Cell Proliferation in Primary Sjögren's Syndrome.Journal of immunology research · 2025Article
- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 2024Review
- mCherry on Top: A Positive Read-Out Cellular Platform for Screening DMD Exon Skipping Xenopeptide-PMO Conjugates.Bioconjugate chemistry · 2023Article
- A novel therapeutic vaccine targeting the soluble TNFα receptor II to limit the progression of cardiovascular disease: AtheroVax™.Frontiers in cardiovascular medicine · 2023Review
- Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids.International journal of molecular sciences · 2021Article
- Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.Frontiers in immunology · 2021Review
- Article
- Alternative pre-mRNA splicing of Toll-like receptor signaling components in peripheral blood mononuclear cells from patients with ARDS.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Article
- Alternative RNA splicing: contribution to pain and potential therapeutic strategy.Drug discovery today · 2016Review
- Splice-switching antisense oligonucleotides as therapeutic drugs.Nucleic acids research · 2016Review
- Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.PloS one · 2016Article
- Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides.Molecular therapy. Nucleic acids · 2014Article
- Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model.The Journal of clinical investigation · 2014Article
- Design and evaluation of locked nucleic acid-based splice-switching oligonucleotides in vitro.Nucleic acids research · 2014Article
- Synthesis and biophysical properties of C5-functionalized LNA (locked nucleic acid).The Journal of organic chemistry · 2014Article
- C5-alkynyl-functionalized α-L-LNA: synthesis, thermal denaturation experiments and enzymatic stability.The Journal of organic chemistry · 2014Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti-TNF-alpha drugs such as etanercept are effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of drugs designed to induce therapeutically favorable splice variants of targeted genes. In this work, we used locked nucleic acid (LNA)-based SSOs to modulate splicing of TNF receptor 2 (TNFR2) pre-mRNA. The SSO induced skipping of TNFR2 exon 7, which codes the transmembrane domain (TM), switching endogenous expression from the membrane-bound, functional form to a soluble, secreted form (Delta7TNFR2). This decoy receptor protein accumulated in the circulation of treated mice, antagonized TNF-alpha, and altered disease in two mouse models: TNF-alpha-induced hepatitis and collagen-induced arthritis (CIA). This is the first report of upregulation of the endogenous, circulating TNF-alpha antagonist by oligonucleotide-induced splicing modulation.
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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.