{"doi":"10.1126/science.ade6967","title":"In vivo hematopoietic stem cell modification by mRNA delivery","abstract":"Hematopoietic stem cells (HSCs) are the source of all blood cells over an individual's lifetime. Diseased HSCs can be replaced with gene-engineered or healthy HSCs through HSC transplantation (HSCT). However, current protocols carry major side effects and have limited access. We developed CD117/LNP-messenger RNA (mRNA), a lipid nanoparticle (LNP) that encapsulates mRNA and is targeted to the stem cell factor receptor (CD117) on HSCs. Delivery of the anti-human CD117/LNP-based editing system yielded near-complete correction of hematopoietic sickle cells. Furthermore, in vivo delivery of pro-apoptotic PUMA (p53 up-regulated modulator of apoptosis) mRNA with CD117/LNP affected HSC function and permitted nongenotoxic conditioning for HSCT. The ability to target HSCs in vivo offers a nongenotoxic conditioning regimen for HSCT, and this platform could be the basis of in vivo genome editing to cure genetic disorders, which would abrogate the need for HSCT.","journal":"Science","year":2023,"id":314901,"datarank":6.6220395761763635,"base_score":5.755742213586912,"endowment":5.755742213586912,"self_citation_contribution":0.863361332038037,"citation_network_contribution":5.758678244138326,"self_endowment_contribution":0.863361332038037,"citer_contribution":5.758678244138326,"corpus_percentile":null,"corpus_rank":null,"citation_count":315,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"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":620138,"name":"Tyler E. Papp","orcid":"0000-0001-5116-0782","position":1,"is_corresponding":false},{"id":745657,"name":"Michael Triebwasser","orcid":"0000-0002-4849-2812","position":2,"is_corresponding":false},{"id":620137,"name":"Amir Yadegari","orcid":"0000-0002-1609-1459","position":3,"is_corresponding":false},{"id":1015520,"name":"Megan T. Fedorky","orcid":null,"position":4,"is_corresponding":false},{"id":1014565,"name":"Naoto Tanaka","orcid":"0000-0001-7312-0239","position":5,"is_corresponding":false},{"id":376404,"name":"Osheiza Abdulmalik","orcid":"0000-0003-2497-4291","position":6,"is_corresponding":false},{"id":711160,"name":"Giulia Pavani","orcid":"0000-0002-2522-2684","position":7,"is_corresponding":false},{"id":969447,"name":"Yongping Wang","orcid":"0000-0003-0357-4918","position":8,"is_corresponding":false},{"id":496143,"name":"Stephan A. Grupp","orcid":"0000-0001-8030-7595","position":9,"is_corresponding":false},{"id":48129,"name":"Stella T. Chou","orcid":"0000-0003-4333-6965","position":10,"is_corresponding":false},{"id":968730,"name":"Houping Ni","orcid":"0009-0007-0635-9603","position":11,"is_corresponding":false},{"id":54907,"name":"Barbara L. Mui","orcid":"0000-0002-3056-6836","position":12,"is_corresponding":false},{"id":54908,"name":"Ying K. Tam","orcid":"0000-0002-4083-5251","position":13,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":14,"is_corresponding":false},{"id":535124,"name":"Stefano Rivella","orcid":"0000-0002-0938-6558","position":15,"is_corresponding":false},{"id":620139,"name":"Hamideh Parhiz","orcid":"0000-0002-2880-2836","position":16,"is_corresponding":false},{"id":1014564,"name":"Laura Breda","orcid":"0000-0003-2133-4432","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:06:02.898877Z","pmid":"37499029","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":[]}