{"doi":"10.1016/j.stem.2024.03.002","title":"A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection","abstract":"Allogeneic hematopoietic stem and progenitor cell transplant (HSCT) of CCR5 null (CCR5Δ32) cells can be curative for HIV-1-infected patients. However, because allogeneic HSCT poses significant risk, CCR5Δ32 matched bone marrow donors are rare, and CCR5Δ32 transplant does not confer resistance to the CXCR4-tropic virus, it is not a viable option for most patients. We describe a targeted Cas9/AAV6-based genome editing strategy for autologous HSCT resulting in both CCR5- and CXCR4-tropic HIV-1 resistance. Edited human hematopoietic stem and progenitor cells (HSPCs) maintain multi-lineage repopulation capacity in vivo, and edited primary human T cells potently inhibit infection by both CCR5-tropic and CXCR4-tropic HIV-1. Modification rates facilitated complete loss of CCR5-tropic replication and up to a 2,000-fold decrease in CXCR4-tropic replication without CXCR4 locus disruption. This multi-factor editing strategy in HSPCs could provide a broad approach for autologous HSCT as a functional cure for both CCR5-tropic and CXCR4-tropic HIV-1 infections.","journal":"Cell stem cell","year":2024,"id":432118,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":1171422,"name":"William N. Feist","orcid":"0000-0002-5870-4460","position":1,"is_corresponding":false},{"id":1237180,"name":"Elena J. Sasu","orcid":null,"position":2,"is_corresponding":false},{"id":738427,"name":"Sofia E. Luna","orcid":"0000-0002-9173-9518","position":3,"is_corresponding":false},{"id":1237181,"name":"Kaya Ben-Efraim","orcid":null,"position":4,"is_corresponding":false},{"id":626398,"name":"Rasmus O. Bak","orcid":"0000-0002-7383-0297","position":5,"is_corresponding":false},{"id":651941,"name":"Alma‐Martina Cepika","orcid":"0000-0003-2862-1901","position":6,"is_corresponding":false},{"id":251111,"name":"Matthew H. Porteus","orcid":"0000-0002-3850-4648","position":7,"is_corresponding":false},{"id":650352,"name":"Amanda M. Dudek","orcid":"0000-0003-0239-3576","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-19T01:59:35.267142Z","pmid":"38579682","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":[]}