{"doi":"10.1101/2020.10.13.338319","title":"Cas9-AAV6 Gene Correction of Beta-Globin in Autologous HSCs Improves Sickle Cell Disease Erythropoiesis in Mice","abstract":"Abstract CRISPR/Cas9-mediated beta-globin ( HBB ) gene correction of Sickle Cell Disease (SCD) patient-derived hematopoietic stem cells (HSCs) in combination with autologous transplantation represents a novel paradigm in gene therapy. Although several Cas9-based HBB -correction approaches have been proposed, functional correction of in vivo erythropoiesis has not been investigated. Here, we used a humanized globin-cluster SCD mouse model to study Cas9-AAV6-mediated HBB -correction in functional HSCs within the context of autologous transplantation. We discover that long-term multipotent HSCs can be gene corrected ex vivo and stable hemoglobin-A production can be achieved in vivo from HBB -corrected HSCs following autologous transplantation. We observed a direct correlation between increased HBB -corrected myeloid chimerism and normalized in vivo RBC features, but even low levels of chimerism resulted in robust hemoglobin-A levels. Moreover, this study offers a platform for gene editing of mouse HSCs for both basic and translational research.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120358,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406444,"name":"Daniel P. Dever","orcid":"0000-0001-5966-4803","position":1,"is_corresponding":false},{"id":557546,"name":"Ron Baik","orcid":"0000-0002-2458-0121","position":2,"is_corresponding":false},{"id":557547,"name":"Joab Camarena","orcid":"0000-0002-3102-5820","position":3,"is_corresponding":false},{"id":557548,"name":"Ian Hsu","orcid":"0000-0002-1648-5060","position":4,"is_corresponding":false},{"id":557549,"name":"Carsten T. Charlesworth","orcid":"0000-0002-8588-6204","position":5,"is_corresponding":false},{"id":557550,"name":"Chika Morita","orcid":"0000-0003-1317-685X","position":6,"is_corresponding":false},{"id":189721,"name":"Hiromitsu Nakauchi","orcid":"0000-0002-9841-6973","position":7,"is_corresponding":false},{"id":251111,"name":"Matthew H. Porteus","orcid":"0000-0002-3850-4648","position":8,"is_corresponding":false},{"id":29458,"name":"Adam C. Wilkinson","orcid":"0000-0001-7406-0151","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:33.640077Z","pmid":null,"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":[]}