{"doi":"10.1016/j.jconrel.2023.11.034","title":"Effective delivery of miR-511-3p with mannose-decorated exosomes with RNA nanoparticles confers protection against asthma","abstract":"Our previous studies have shown that miR-511-3p treatment has a beneficial effect in alleviating allergic airway inflammation. Here, we sought to explore its therapeutic potential in animal models and gain a deeper understanding of its therapeutic value for asthma. miR-511-3p knockout mice (miR-511-3p−/−) were generated by CRISPR/Cas and showed exacerbated airway hyper-responsiveness and Th2-associated allergic airway inflammation compared with wild-type (WT) mice after exposed to cockroach allergen. RNA nanoparticles with mannose decorated EV-miR-511-3p were also created by loading miR-511-3p mimics into the mannose decorated EVs with engineered RNA nanoparticle PRNA-3WJ (Man-EV-miR-511-3p). Intra-tracheal inhalation of Man-EV-miR-511-3p, which could effectively penetrate the airway mucus barrier and deliver functional miR-511-3p to lung macrophages, successfully reversed the increased airway inflammation observed in miR-511-3p−/− mice. Through microarray analysis, complement C3 (C3) was identified as one of the major targets of miR-511-3p. C3 was increased in LPS-treated macrophages but decreased after miR-511-3p treatment. Consistent with these findings, C3 expression was elevated in the lung macrophages of an asthma mouse model but decreased in mice treated with miR-511-3p. Further experiments, including miRNA-mRNA pulldown and luciferase reporter assays, confirmed that miR-511-3p directly binds to C3 and activates the C3 gene. Thus, miR-511-3p represents a promising therapeutic target for asthma, and RNA nanotechnology reprogrammed EVs are efficient carriers for miRNA delivery for disease treatment.","journal":"Journal of Controlled Release","year":2023,"id":322306,"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":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"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":311772,"name":"Xinyue Hu","orcid":"0000-0002-2508-121X","position":1,"is_corresponding":false},{"id":901702,"name":"Rongjun Wan","orcid":"0000-0003-2643-3173","position":2,"is_corresponding":false},{"id":699784,"name":"Xiaojun Xiao","orcid":"0000-0002-1195-0541","position":3,"is_corresponding":false},{"id":666097,"name":"Ying‐Chun Shen","orcid":"0000-0001-8426-9071","position":4,"is_corresponding":false},{"id":1024581,"name":"Prakhyath Srikaram","orcid":"0000-0002-2857-0545","position":5,"is_corresponding":false},{"id":1035852,"name":"Sai Nithin Avvaru","orcid":"0009-0002-1593-8352","position":6,"is_corresponding":false},{"id":1035853,"name":"Fuhan Yang","orcid":"0000-0003-1781-1515","position":7,"is_corresponding":false},{"id":953718,"name":"Fengmei Pi","orcid":null,"position":8,"is_corresponding":false},{"id":1035854,"name":"Yufeng Zhou","orcid":"0000-0002-6050-4951","position":9,"is_corresponding":false},{"id":242481,"name":"Mei Wan","orcid":"0000-0001-9404-540X","position":10,"is_corresponding":false},{"id":242478,"name":"Peisong Gao","orcid":"0000-0002-7651-1339","position":11,"is_corresponding":false},{"id":1016478,"name":"Wei Tu","orcid":"0000-0002-0255-4037","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:07:42.497873Z","pmid":"37996055","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":[]}