{"doi":"10.1016/j.omtm.2023.08.016","title":"Efficient gene transduction in pigs and macaques with the engineered AAV vector AAV.GT5 for hemophilia B gene therapy","abstract":null,"journal":"Molecular Therapy - Methods & Clinical Development","year":2023,"id":598722,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1534399,"name":"Kazuhiro Endo","orcid":null,"position":1,"is_corresponding":false},{"id":1534400,"name":"Atsushi Ugajin","orcid":null,"position":2,"is_corresponding":false},{"id":1534402,"name":"Tomohiro Kikuchi","orcid":null,"position":3,"is_corresponding":false},{"id":1534404,"name":"Shuji Hishikawa","orcid":null,"position":4,"is_corresponding":false},{"id":1534405,"name":"Hitoyasu Nakamura","orcid":null,"position":5,"is_corresponding":false},{"id":1534406,"name":"Yuko Katakai","orcid":null,"position":6,"is_corresponding":false},{"id":1534408,"name":"Nemekhbayar Baatartsogt","orcid":null,"position":7,"is_corresponding":false},{"id":1534410,"name":"Takafumi Hiramoto","orcid":null,"position":8,"is_corresponding":false},{"id":1534412,"name":"Morisada Hayakawa","orcid":null,"position":9,"is_corresponding":false},{"id":1534414,"name":"Nobuhiko Kamoshita","orcid":null,"position":10,"is_corresponding":false},{"id":1534416,"name":"Shoji Yamazaki","orcid":null,"position":11,"is_corresponding":false},{"id":1534417,"name":"Akihiro Kume","orcid":null,"position":12,"is_corresponding":false},{"id":1534420,"name":"Harushi Mori","orcid":null,"position":13,"is_corresponding":false},{"id":1534422,"name":"Naohiro Sata","orcid":null,"position":14,"is_corresponding":false},{"id":1534424,"name":"Yoichi Sakata","orcid":null,"position":15,"is_corresponding":false},{"id":151484,"name":"Shin-ichi Muramatsu","orcid":null,"position":16,"is_corresponding":false},{"id":1479973,"name":"Tsukasa Ohmori","orcid":"0000-0001-5082-6394","position":17,"is_corresponding":false},{"id":1534398,"name":"Yuji Kashiwakura","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Efficient gene transduction in pigs and macaques with the engineered AAV vector AAV.GT5 for hemophilia B gene therapy","abstract":"Gene therapy using adeno-associated virus (AAV)-based vectors has become a realistic therapeutic option for hemophilia. We examined the potential of a novel engineered liver-tropic AAV3B-based vector, AAV.GT5, for hemophilia B gene therapy. In vitro transduction with AAV.GT5 in human hepatocytes was more than 100 times higher than with AAV-Spark100, another bioengineered vector used in a clinical trial. However, liver transduction following intravenous injection of these vectors was similar in mice with a humanized liver and in macaques. This discrepancy was due to the low recovery and short half-life of AAV.GT5 in blood, depending on the positive charge of the heparin-binding site in the capsid. Bypassing systemic clearance with the intra-hepatic vascular administration of AAV.GT5, but not AAV-Spark100, enhanced liver transduction in pigs and macaques. AAV.GT5 did not develop neutralizing antibodies (NAbs) in two of four animals, while AAV-Spark100 induced serotype-specific NAbs in all macaques tested (4 of 4). The NAbs produced after AAV-Spark100 administration were relatively serotype specific, and challenge with AAV.GT5 through the hepatic artery successfully boosted liver transduction in one animal previously administered AAV-Spark100. In summary, AAV.GT5 showed different vector kinetics and NAb induction compared with AAV-Spark100, and intra-hepatic vascular administration may minimize the vector dose required and vector dissemination.","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37693948","pmcid":"PMC10491835","openalex_id":"https://openalex.org/W4386052789","authors":[],"funders":[{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"JP18pc0101030","title":null}],"total_grants":1,"fwci":2.4024,"citation_percentile":0.89565944,"influential_citations":0,"citation_trend":[{"year":2024,"count":4},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1016/j.omtm.2023.08.016","host_type":"journal"},{"url":"https://doi.org/10.1016/j.omtm.2023.08.016","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2329050123001304?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2329050123001304?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37693948","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10491835","host_type":"repository"},{"url":"https://doaj.org/article/e60d3f3fd02c459c99665b37f69364fb","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10491835/pdf/main.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10491835","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10491835?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Virus-based gene therapy research","Viral Infectious Diseases and Gene Expression in Insects","CRISPR and Genetic Engineering"],"mesh_terms":[],"keywords":["Transduction (biophysics)","Genetic enhancement","Adeno-associated virus","Virology","Capsid","Vector (molecular biology)","Virus","Medicine","Gene delivery","Viral vector","Biology","Gene","Immunology","Recombinant DNA","Gene therapy","Hemophilia B","Adeno-associated Virus Vectors","Vector Recoverability","Intra-Hepatic Vascular Administration"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T16:08:59.351701Z","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":[]}