{"doi":"10.1016/j.xcrm.2025.102475","title":"Complete neutralizing antibody evasion by serodivergent non-mammalian AAVs enables gene therapy redosing","abstract":"The use of adeno-associated virus (AAV) as a gene therapy vector is significantly limited by pre-existing immunity. The high seroprevalence and broad antigenic cross-reactivity of primate-derived AAVs restrict patient eligibility and preclude therapeutic redosing. Here, we harness the phylogenetic diversity of non-mammalian dependoparvoviruses to engineer serologically distinct AAV capsids for immune evasion. A barcoded screen of divergent Dependoparvovirus isolates identifies AAV.div3A, a chimeric capsid with robust transduction, zero antigenic cross-reactivity, and undetectable seroprevalence. Derived from a phylogenetically distant Muscovy duck isolate, AAV.div3A fully evades neutralization in mice, even after passive immunization with NAb+ human serum or following initial vector dosing. Further engineering yields AAV.div3A-M1, a myotropic, liver-detargeted capsid with enhanced cardiac and diaphragm transduction. In a Pompe disease model, redosing with AAV.div3A or div3A-M1 significantly increases therapeutic GAA levels. Overall, our work leverages untapped dependoparvoviral diversity to overcome pre-existing and vector-induced immunity, enabling expansion of patient eligibility and effective redosing.","journal":"Cell Reports Medicine","year":2025,"id":522391,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1394418,"name":"Sophia Fergione","orcid":null,"position":1,"is_corresponding":false},{"id":1027982,"name":"Vivian Yudistyra","orcid":"0000-0001-8583-9232","position":2,"is_corresponding":false},{"id":269027,"name":"Marco M. Fanous","orcid":null,"position":3,"is_corresponding":false},{"id":932637,"name":"Abigail R. Benkert","orcid":"0000-0001-5220-7706","position":4,"is_corresponding":false},{"id":323797,"name":"Delaney G. Fisher","orcid":"0000-0002-1876-4733","position":5,"is_corresponding":false},{"id":370486,"name":"Joshua A. Hull","orcid":null,"position":6,"is_corresponding":false},{"id":373519,"name":"Mai K. ElMallah","orcid":"0000-0002-1775-1156","position":7,"is_corresponding":false},{"id":265976,"name":"Aravind Asokan","orcid":"0000-0001-5563-4877","position":8,"is_corresponding":false},{"id":1215348,"name":"E. Loeb","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41308640","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":[]}