{"doi":"10.1038/s41587-024-02437-3","title":"Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein","abstract":"Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP-LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP-LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16‒37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP-LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP-LNP complexes can expand the therapeutic potential of genome editing.","journal":"Nature Biotechnology","year":2024,"id":416531,"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":127,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"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":492016,"name":"Hesong Han","orcid":"0000-0001-5545-5238","position":1,"is_corresponding":false},{"id":1200870,"name":"Sheng Zhao","orcid":"0009-0002-9890-048X","position":2,"is_corresponding":false},{"id":1160832,"name":"Bryant Xu","orcid":null,"position":3,"is_corresponding":false},{"id":1009825,"name":"Boyan Yin","orcid":"0000-0002-9023-6265","position":4,"is_corresponding":false},{"id":688087,"name":"Atip Lawanprasert","orcid":"0009-0001-3163-8803","position":5,"is_corresponding":false},{"id":849169,"name":"Marena Trinidad","orcid":"0000-0001-7839-4642","position":6,"is_corresponding":false},{"id":1160196,"name":"Benjamin W. Burgstone","orcid":"0009-0000-8256-3867","position":7,"is_corresponding":false},{"id":235839,"name":"Niren Murthy","orcid":"0000-0002-7815-7337","position":8,"is_corresponding":false},{"id":2407,"name":"Jennifer A. Doudna","orcid":"0000-0001-9161-999X","position":9,"is_corresponding":false},{"id":764145,"name":"Kai Chen","orcid":"0000-0002-3325-3536","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T01:56:44.873714Z","pmid":"39415058","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":[]}