{"doi":"10.4049/jimmunol.2200550","title":"Antisense Oligonucleotide Therapy Decreases IL-1β Expression and Prolongs Survival in Mutant <i>Nlrp3</i> Mice","abstract":"Antisense oligonucleotides (ASOs) are a novel therapeutic strategy that targets a specific gene and suppresses its expression. The cryopyrin-associated periodic syndromes (CAPS) are a spectrum of autoinflammatory diseases characterized by systemic and tissue inflammation that is caused by heterozygous gain-of-function mutations in the nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) gene. The aim of this study was to investigate the efficacy of an Nlrp3-specific ASO treatment in CAPS. An Nlrp3-specific ASO was designed and tested in murine cell lines and bone marrow-derived macrophages (BMDMs) from wild-type and CAPS mouse models. Nlrp3 knock-in mice were treated in vivo with Nlrp3-specific ASO, survival was monitored, and expression of organ-specific Nlrp3 and IL-1β was measured. Nlrp3-specific ASO treatment of murine cell lines and BMDMs showed a significant downregulation of Nlrp3 and mature IL-1β protein expression. Ex vivo treatment of Nlrp3 mutant mouse-derived BMDMs with Nlrp3-specific ASO demonstrated significantly reduced IL-1β release. In vivo, Nlrp3-specific ASO treatment of Nlrp3 mutant mice prolonged survival, reduced systemic inflammation, and decreased tissue-specific expression of Nlrp3 and mature IL-1β protein. The results of this study demonstrate that Nlrp3-specific ASO treatment downregulates Nlrp3 expression and IL-1β release in CAPS models, suggesting ASO therapy as a potential treatment of CAPS and other NLRP3-mediated diseases.","journal":"The Journal of Immunology","year":2023,"id":360723,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":794185,"name":"Marta de los Reyes Jiménez","orcid":"0000-0003-1087-8100","position":1,"is_corresponding":false},{"id":369678,"name":"Laela M. Booshehri","orcid":"0000-0003-0175-9468","position":2,"is_corresponding":false},{"id":870123,"name":"Janset Onyuru","orcid":"0000-0003-3924-8487","position":3,"is_corresponding":false},{"id":226030,"name":"Aleksandra Leszczynska","orcid":"0000-0002-8005-2657","position":4,"is_corresponding":false},{"id":1112963,"name":"Anna Uri","orcid":null,"position":5,"is_corresponding":false},{"id":1112525,"name":"Sven Michel","orcid":"0000-0003-3604-3187","position":6,"is_corresponding":false},{"id":1112526,"name":"Richard Klar","orcid":"0000-0001-6625-794X","position":7,"is_corresponding":false},{"id":1112964,"name":"Frank Jaschinski","orcid":null,"position":8,"is_corresponding":false},{"id":302637,"name":"Ariel E. Feldstein","orcid":"0000-0001-7202-3840","position":9,"is_corresponding":false},{"id":339566,"name":"Lori Broderick","orcid":"0000-0001-6147-7097","position":10,"is_corresponding":false},{"id":226040,"name":"Hal M. Hoffman","orcid":"0000-0001-8609-2548","position":11,"is_corresponding":false},{"id":226032,"name":"Benedikt Kaufmann","orcid":"0000-0002-8141-9676","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:14:06.433417Z","pmid":"37256266","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":[]}