{"doi":"10.1016/j.omtn.2023.07.016","title":"VWA3A-derived ependyma promoter drives increased therapeutic protein secretion into the CSF","abstract":"Recombinant adeno-associated viral vectors (rAAVs) are a promising strategy to treat neurodegenerative diseases because of their ability to infect non-dividing cells and confer long-term transgene expression. Despite an ever-growing library of capsid variants, widespread delivery of AAVs in the adult central nervous system remains a challenge. We have previously demonstrated successful distribution of secreted proteins by infection of the ependyma, a layer of post-mitotic epithelial cells lining the ventricles of the brain and central column of the spinal cord, and subsequent protein delivery via the cerebrospinal fluid (CSF). Here we define a functional ependyma promoter to enhance expression from this cell type. Using RNA sequencing on human autopsy samples, we identified disease- and age-independent ependyma gene signatures. Associated promoters were cloned and screened as libraries in mouse and rhesus macaque to reveal cross-species function of a human DNA-derived von Willebrand factor domain containing 3A ( VWA3A ) promoter. When tested in mice, our VWA3A promoter drove strong, ependyma-localized expression of eGFP and increased secreted ApoE protein levels in the CSF by 2–12× over the ubiquitous iCAG promoter.","journal":"Molecular Therapy — Nucleic Acids","year":2023,"id":362502,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":1058920,"name":"Yong Hong Chen","orcid":null,"position":1,"is_corresponding":false},{"id":727929,"name":"Paul T. Ranum","orcid":null,"position":2,"is_corresponding":false},{"id":552366,"name":"Stephanie L. Coffin","orcid":"0000-0002-9119-0377","position":3,"is_corresponding":false},{"id":229073,"name":"Larry N. Singh","orcid":"0000-0002-2478-5864","position":4,"is_corresponding":false},{"id":817369,"name":"Luis Tecedor","orcid":null,"position":5,"is_corresponding":false},{"id":752936,"name":"Megan S. Keiser","orcid":null,"position":6,"is_corresponding":false},{"id":228740,"name":"Eloïse Hudry","orcid":"0000-0003-3654-9663","position":7,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":8,"is_corresponding":false},{"id":348292,"name":"Beverly L. Davidson","orcid":"0000-0002-3715-6290","position":9,"is_corresponding":false},{"id":1115656,"name":"Ellie M. Carrell","orcid":"0000-0001-5222-5437","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:19.266946Z","pmid":"37547292","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":[]}