{"doi":"10.1073/pnas.2211977120","title":"A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis","abstract":"Engineered microbes for the delivery of biologics are a promising avenue for the treatment of various conditions such as chronic inflammatory disorders and metabolic disease. In this study, we developed a genetically engineered probiotic delivery system that delivers a peptide to the intestinal tract with high efficacy. We constructed an inducible system in the probiotic Lactobacillus reuteri to secrete the Kv1.3 potassium blocker ShK-235 (LrS235). We show that LrS235 culture supernatants block Kv1.3 currents and preferentially inhibit human T effector memory (T EM ) lymphocyte proliferation in vitro. A single oral gavage of healthy rats with LrS235 resulted in sufficient functional ShK-235 in the circulation to reduce inflammation in a delayed-type hypersensitivity model of atopic dermatitis mediated by T EM cells. Furthermore, the daily oral gavage of LrS235 dramatically reduced clinical signs of disease and joint inflammation in rats with a model of rheumatoid arthritis without eliciting immunogenicity against ShK-235. This work demonstrates the efficacy of using the probiotic L. reuteri as a novel oral delivery platform for the peptide ShK-235 and provides an efficacious strategy to deliver other biologics with great translational potential.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":324886,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":577669,"name":"Duolong Zhu","orcid":"0000-0002-8048-2171","position":1,"is_corresponding":false},{"id":378267,"name":"Laura Ortiz-Velez","orcid":"0000-0002-2096-1795","position":2,"is_corresponding":false},{"id":295678,"name":"Jacob L. Perry","orcid":"0000-0002-0630-9266","position":3,"is_corresponding":false},{"id":1004989,"name":"Michael W. Pennington","orcid":"0000-0001-5446-3447","position":4,"is_corresponding":false},{"id":255993,"name":"Joseph M. Hyser","orcid":"0000-0001-5249-3482","position":5,"is_corresponding":false},{"id":255992,"name":"Robert A. Britton","orcid":"0000-0001-8983-9539","position":6,"is_corresponding":false},{"id":241983,"name":"Christine Beeton","orcid":"0000-0002-2500-5874","position":7,"is_corresponding":false},{"id":1004988,"name":"Yuqing Wang","orcid":"0000-0003-4382-7617","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:16.809511Z","pmid":"36595694","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":[]}