{"doi":"10.17615/574j-dp62","title":"An Endogenous TNF-α Antagonist Induced by Splice-switching Oligonucleotides Reduces Inflammation in Hepatitis and Arthritis Mouse Models","abstract":"Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti–TNF-α 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 (Δ7TNFR2). This decoy receptor protein accumulated in the circulation of treated mice, antagonized TNF-α, and altered disease in two mouse models: TNF-α-induced hepatitis and collagen-induced arthritis (CIA). This is the first report of upregulation of the endogenous, circulating TNF-α antagonist by oligonucleotide-induced splicing modulation.","journal":"UNC Libraries","year":2020,"id":142784,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":609907,"name":"Henrik Steen Hansen","orcid":"0000-0001-6477-9832","position":1,"is_corresponding":false},{"id":610342,"name":"LeShara Fulton","orcid":null,"position":2,"is_corresponding":false},{"id":610343,"name":"Henrik Ørum","orcid":null,"position":3,"is_corresponding":false},{"id":546749,"name":"Teresa K. Tarrant","orcid":"0000-0003-4067-5363","position":4,"is_corresponding":false},{"id":610344,"name":"Maria A Graziewicz","orcid":null,"position":5,"is_corresponding":false},{"id":592353,"name":"Jennifer Roberts","orcid":"0000-0003-4552-9576","position":6,"is_corresponding":false},{"id":579850,"name":"Ryszard Kole","orcid":null,"position":7,"is_corresponding":false},{"id":353568,"name":"Brian Buckley","orcid":"0000-0001-7336-4321","position":8,"is_corresponding":false},{"id":593139,"name":"Peter Sazani","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:34.768426Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}