{"doi":"10.1101/2020.06.16.152975","title":"Broad gene expression throughout the mouse and marmoset brain after intravenous delivery of engineered AAV capsids","abstract":"ABSTRACT Genetic intervention is increasingly explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies relies upon expressing a transgene in affected cells while minimizing off-target expression. To achieve organ/cell-type specific targeting after intravenous delivery of viral vectors, we employed a Cre-transgenic-based screening platform for fast and efficient capsid selection, paired with sequential engineering of multiple surface-exposed loops. We identified capsid variants that are enriched in the brain and detargeted from the liver in mice. The improved enrichment in the brain extends to non-human primates, enabling robust, non-invasive gene delivery to the marmoset brain following IV administration. Importantly, the capsids identified display non-overlapping cell-type tropisms within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood–brain barrier with cell-type specificity in rodents and non-human primates enables new avenues for basic research and potential therapeutic interventions unattainable with naturally occurring serotypes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119800,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556657,"name":"Nick Goeden","orcid":null,"position":1,"is_corresponding":false},{"id":555881,"name":"David Goertsen","orcid":"0000-0001-7138-1697","position":2,"is_corresponding":false},{"id":349526,"name":"Alexander Cummins","orcid":null,"position":3,"is_corresponding":false},{"id":481504,"name":"James Pickel","orcid":"0000-0002-3617-3072","position":4,"is_corresponding":false},{"id":228771,"name":"Viviana Gradinaru","orcid":"0000-0001-5868-348X","position":5,"is_corresponding":false},{"id":555880,"name":"Nicholas C. Flytzanis","orcid":"0000-0002-7921-9392","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:14:13.002105Z","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":[]}