{"doi":"10.1016/j.omtm.2023.03.008","title":"HDAd6/35++ - A new helper-dependent adenovirus vector platform for in vivo transduction of hematopoietic stem cells","abstract":"In previous studies, we achieved safe and efficient in vivo hematopoietic stem cell (HSC) transduction in mobilized mice and macaques with intravenously injected helper-dependent adenovirus HDAd5/35++ vectors. These vectors are derivatives of serotype Ad5-containing CD46-affinity enhanced Ad35 fiber knob domains. Considering the impact of anti-Ad5/HDAd5/35++ neutralizing serum antibodies present in the human population, we generated HSC-retargeted HDAd6/35++ vectors derived from serotype 6. We found a lower prevalence and titers of serum anti-HDAd6/35++ in human samples compared with HDAd5/35++. HDAd6/35++ vectors efficiently transduced human and rhesus CD34 + cells in vitro . Intravenous injection of HDAd5/35++-GFP or HDAd6/35++-GFP vectors after G-CSF/AMD3100 mobilization of mice with established human hematopoiesis or human CD46 transgenic mice resulted in comparable GFP marking rates in HSCs in the bone marrow and spleen. In long-term in vivo HSC transduction and selection studies with integrating vectors, stable GFP expression in >75% of PBMCs was show for both vectors. In contrast with HDAd5/35++, undesired transduction of hepatocytes was minimal with HDAd6/35++. Furthermore, HDAd6/35++ allowed for efficient in vivo HSC transduction in Ad5-pre-immune mice. These features, together with the straightforward production of HDAd6/35++ vectors at high yield, make this new HDAd vector platform attractive for clinical translation of the in vivo approach.","journal":"Molecular Therapy — Methods & Clinical Development","year":2023,"id":333737,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"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":309008,"name":"Aphrodite Georgakopoulou","orcid":"0000-0003-1541-7549","position":1,"is_corresponding":false},{"id":795422,"name":"Wenli Zhang","orcid":"0000-0002-6243-6286","position":2,"is_corresponding":false},{"id":490051,"name":"Jiho Kim","orcid":"0000-0001-5301-8130","position":3,"is_corresponding":false},{"id":310090,"name":"Sucheol Gil","orcid":null,"position":4,"is_corresponding":false},{"id":1061514,"name":"Anja Ehrhardt","orcid":"0000-0002-6639-4888","position":5,"is_corresponding":false},{"id":206224,"name":"Andre Lieber","orcid":"0000-0001-6742-6266","position":6,"is_corresponding":false},{"id":309007,"name":"Hongjie Wang","orcid":"0000-0002-4359-5417","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:44.297718Z","pmid":"37081854","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":[]}