{"doi":"10.1101/2022.03.22.485401","title":"Inhalable polymer nanoparticles for versatile mRNA delivery and mucosal vaccination","abstract":"An inhalable platform for mRNA therapeutics would enable minimally invasive and lung targeted delivery for a host of pulmonary diseases. Development of lung targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine-co-ester) polyplexes for mRNA delivery using end group modifications and polyethylene glycol. Our polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for SARS-CoV-2. Intranasal vaccination with spike protein mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected K18-hACE2 mice from lethal viral challenge. One-sentence summary: Inhaled polymer nanoparticles (NPs) achieve high mRNA expression in the lung and induce protective immunity against SARS-CoV-2.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":296778,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":643216,"name":"Molly K. Grun","orcid":"0000-0003-3789-1890","position":1,"is_corresponding":false},{"id":105757,"name":"Tianyang Mao","orcid":"0000-0001-9251-8592","position":2,"is_corresponding":false},{"id":105753,"name":"Benjamin Israelow","orcid":"0000-0002-1308-8246","position":3,"is_corresponding":false},{"id":305500,"name":"Melanie Reschke","orcid":"0000-0003-1902-5876","position":4,"is_corresponding":false},{"id":868806,"name":"Julian Grundler","orcid":"0000-0003-4848-713X","position":5,"is_corresponding":false},{"id":984078,"name":"Laiba Akhtar","orcid":"0009-0009-2589-8519","position":6,"is_corresponding":false},{"id":643218,"name":"Teresa Lee","orcid":"0000-0001-9960-0767","position":7,"is_corresponding":false},{"id":643217,"name":"Kwangsoo Shin","orcid":"0000-0001-5337-0679","position":8,"is_corresponding":false},{"id":243177,"name":"Alexandra S. Piotrowski-Daspit","orcid":"0000-0003-4555-3234","position":9,"is_corresponding":false},{"id":41685,"name":"Robert Homer","orcid":"0000-0002-2055-5885","position":10,"is_corresponding":false},{"id":105840,"name":"Akiko Iwasaki","orcid":"0000-0002-7824-9856","position":11,"is_corresponding":false},{"id":694346,"name":"Hee‐Won Suh","orcid":null,"position":12,"is_corresponding":false},{"id":243179,"name":"W. Mark Saltzman","orcid":"0000-0002-2163-549X","position":13,"is_corresponding":false},{"id":983127,"name":"Alexandra Suberi","orcid":"0000-0003-3180-0935","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T00:31:21.257700Z","pmid":"35350207","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":[]}