{"doi":"10.1101/2024.03.08.583956","title":"Combining Cell-Intrinsic and -Extrinsic Resistance to HIV-1 By Engineering Hematopoietic Stem Cells for CCR5 Knockout and B Cell Secretion of Therapeutic Antibodies","abstract":"Abstract Autologous transplantation of CCR5 null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment is limited because of the rarity of CCR5 -null matched donors, the morbidities associated with allogeneic transplantation, and the prevalence of HIV-1 strains resistant to CCR5 knockout (KO) alone. Here, we propose a one-time therapy through autologous transplantation of HSPCs genetically engineered ex vivo to produce both CCR5 KO cells and long-term secretion of potent HIV-1 inhibiting antibodies from B cell progeny. CRISPR-Cas9-engineered HSPCs maintain engraftment capacity and multi-lineage potential in vivo and can be engineered to express multiple antibodies simultaneously. Human B cells engineered to express each antibody secrete neutralizing concentrations capable of inhibiting HIV-1 pseudovirus infection in vitro . This work lays the groundwork for a potential one-time functional cure for HIV-1 through combining the long-term delivery of therapeutic antibodies against HIV-1 and the known efficacy of CCR5 KO HSPC transplantation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490259,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"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":738427,"name":"Sofia E. Luna","orcid":"0000-0002-9173-9518","position":1,"is_corresponding":false},{"id":1237181,"name":"Kaya Ben-Efraim","orcid":null,"position":2,"is_corresponding":false},{"id":567705,"name":"Maria V. Filsinger Interrante","orcid":"0000-0002-7728-799X","position":3,"is_corresponding":false},{"id":1335653,"name":"Nelson A. Amorin","orcid":null,"position":4,"is_corresponding":false},{"id":1335654,"name":"Nicole M. Johnston","orcid":null,"position":5,"is_corresponding":false},{"id":753426,"name":"Theodora U. J. Bruun","orcid":"0000-0002-7462-2537","position":6,"is_corresponding":false},{"id":704891,"name":"Hana Y. Ghanim","orcid":"0000-0002-4102-2367","position":7,"is_corresponding":false},{"id":274573,"name":"Benjamin J. Lesch","orcid":"0000-0002-2511-3517","position":8,"is_corresponding":false},{"id":650352,"name":"Amanda M. Dudek","orcid":"0000-0003-0239-3576","position":9,"is_corresponding":false},{"id":251111,"name":"Matthew H. Porteus","orcid":"0000-0002-3850-4648","position":10,"is_corresponding":false},{"id":1171422,"name":"William N. Feist","orcid":"0000-0002-5870-4460","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38496600","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":[]}