{"doi":"10.1016/j.ymthe.2023.10.023","title":"Targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells in vivo using the engineered AVID adenovirus vector platform","abstract":"Targeted delivery and cell-type-specific expression of gene-editing proteins in various cell types in vivo represent major challenges for all viral and non-viral delivery platforms developed to date. Here, we describe the development and analysis of artificial vectors for intravascular delivery (AVIDs), an engineered adenovirus-based gene delivery platform that allows for highly targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells (HSPCs) in vivo after intravenous vector administration. Due to a set of refined structural modifications, intravenous administration of AVIDs did not trigger cytokine storm, hepatotoxicity, or thrombocytopenia. Single intravenous administration of AVIDs to humanized mice, grafted with human CD34 + cells, led to up to 20% transduction of CD34 + CD38 − CD45RA − HSPC subsets in the bone marrow. Importantly, targeted in vivo transduction of CD34 + CD38 − CD45RA − CD90 − CD49f + subsets, highly enriched for human hematopoietic stem cells (HSCs), reached up to 19%, which represented a 1,900-fold selectivity in gene delivery to HSC-enriched over lineage-committed CD34-negative cell populations. Because the AVID platform allows for regulated, cell-type-specific expression of gene-editing technologies as well as expression of immunomodulatory proteins to ensure persistence of corrected HSCs in vivo , the HSC-targeted AVID platform may enable development of curative therapies through in vivo gene correction in human HSCs after a single intravenous administration.","journal":"Molecular Therapy","year":2023,"id":337744,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"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":290768,"name":"Svetlana Atasheva","orcid":"0000-0002-7816-393X","position":1,"is_corresponding":false},{"id":829349,"name":"Nicole Wagner","orcid":"0000-0002-1568-6936","position":2,"is_corresponding":false},{"id":1070176,"name":"Nelson C. Di Paolo","orcid":null,"position":3,"is_corresponding":false},{"id":290771,"name":"Phoebe L. Stewart","orcid":"0000-0002-5980-4797","position":4,"is_corresponding":false},{"id":290772,"name":"Dmitry M. Shayakhmetov","orcid":"0000-0002-8320-9007","position":5,"is_corresponding":false},{"id":290769,"name":"Jia Yao","orcid":"0000-0003-3235-5351","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:10:31.133446Z","pmid":"37919899","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":[]}