{"doi":"10.1101/2023.12.20.572615","title":"An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery","abstract":"Abstract Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an AAV capsid, BI-hTFR1, that binds human Transferrin Receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40–50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1 , mutations of which cause Gaucher disease and are linked to Parkinson’s disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9. These findings establish BI-hTFR1 as a promising vector for human CNS gene therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390879,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":983647,"name":"Ken Y. Chan","orcid":"0000-0002-8853-5186","position":1,"is_corresponding":false},{"id":1163117,"name":"Shan Lou","orcid":"0000-0002-1638-9917","position":2,"is_corresponding":false},{"id":985310,"name":"Casey Keyes","orcid":"0000-0001-8763-0221","position":3,"is_corresponding":false},{"id":297708,"name":"Jason Wu","orcid":"0000-0003-3036-9928","position":4,"is_corresponding":false},{"id":1163118,"name":"Nuria Roxana Botticello-Romero","orcid":"0009-0009-5866-177X","position":5,"is_corresponding":false},{"id":985945,"name":"Qingxia Zheng","orcid":null,"position":6,"is_corresponding":false},{"id":985948,"name":"Jencilin Johnston","orcid":null,"position":7,"is_corresponding":false},{"id":1163119,"name":"A. A. Mills","orcid":"0000-0003-3056-7764","position":8,"is_corresponding":false},{"id":985946,"name":"Pamela P. Brauer","orcid":null,"position":9,"is_corresponding":false},{"id":756663,"name":"Gabrielle Clouse","orcid":null,"position":10,"is_corresponding":false},{"id":854053,"name":"Simon Pacouret","orcid":null,"position":11,"is_corresponding":false},{"id":452831,"name":"John W. Harvey","orcid":"0000-0002-6125-0041","position":12,"is_corresponding":false},{"id":1023537,"name":"Thomas Beddow","orcid":null,"position":13,"is_corresponding":false},{"id":567394,"name":"Jenna K. Hurley","orcid":"0009-0005-4477-853X","position":14,"is_corresponding":false},{"id":985309,"name":"Isabelle G. Tobey","orcid":"0000-0001-5428-3809","position":15,"is_corresponding":false},{"id":985947,"name":"Megan Powell","orcid":null,"position":16,"is_corresponding":false},{"id":985308,"name":"Albert T. Chen","orcid":"0000-0002-5387-0208","position":17,"is_corresponding":false},{"id":1023536,"name":"Andrew J. Barry","orcid":null,"position":18,"is_corresponding":false},{"id":12308,"name":"Fatma-Elzahraa Eid","orcid":"0000-0002-6822-9536","position":19,"is_corresponding":false},{"id":985312,"name":"Yujia A. Chan","orcid":"0000-0002-0731-637X","position":20,"is_corresponding":false},{"id":245910,"name":"Benjamin E. Deverman","orcid":"0000-0002-6223-9303","position":21,"is_corresponding":false},{"id":108781,"name":"Qin Huang","orcid":"0000-0003-4139-3819","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"38187643","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":[]}