{"doi":"10.1126/science.adk9428","title":"In vivo editing of lung stem cells for durable gene correction in mice","abstract":"In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.","journal":"Science","year":2024,"id":416333,"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":166,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":636496,"name":"Sumanta Chatterjee","orcid":"0000-0002-6832-0073","position":1,"is_corresponding":false},{"id":840695,"name":"Xizhen Lian","orcid":null,"position":2,"is_corresponding":false},{"id":598761,"name":"Zachary Traylor","orcid":"0000-0002-8997-4674","position":3,"is_corresponding":false},{"id":414224,"name":"Sandhya Ramani Sattiraju","orcid":"0009-0005-9824-8294","position":4,"is_corresponding":false},{"id":846549,"name":"Yufen Xiao","orcid":"0000-0002-5604-7479","position":5,"is_corresponding":false},{"id":1013869,"name":"Sean A. 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