{"doi":"10.1073/pnas.2418024121","title":"Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord","abstract":"Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression. Subsequent testing of these candidates identified two CREs that confer MN-selective gene expression in the spinal cord as well as reduced off-target expression in dorsal root ganglia. Within one of these candidate elements, we identified a compact core transcription factor (TF)-binding region that drives MN-selective gene expression. Finally, we demonstrated that selective spinal cord expression driven by this mouse CRE is preserved in non-human primates. These findings suggest that cell-type-selective viral reagents in which cell-type-selective CREs drive restricted gene expression will be valuable research tools in mice and other mammalian species, with potentially significant therapeutic value in humans.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":464501,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1295813,"name":"Spencer Price","orcid":null,"position":1,"is_corresponding":false},{"id":848530,"name":"Kristina Wang","orcid":"0000-0002-5442-3071","position":2,"is_corresponding":false},{"id":554190,"name":"Stanley Gill","orcid":"0000-0001-5430-4550","position":3,"is_corresponding":false},{"id":1295501,"name":"Erika Ren","orcid":"0009-0009-7861-1139","position":4,"is_corresponding":false},{"id":1295814,"name":"Lorna Jayne","orcid":null,"position":5,"is_corresponding":false},{"id":1295815,"name":"Victoria Pajak","orcid":null,"position":6,"is_corresponding":false},{"id":1295816,"name":"Sarah Deighan","orcid":null,"position":7,"is_corresponding":false},{"id":637001,"name":"Bin Liu","orcid":"0000-0003-2184-4723","position":8,"is_corresponding":false},{"id":846142,"name":"Xiaodong Lü","orcid":"0000-0003-0144-2639","position":9,"is_corresponding":false},{"id":1295502,"name":"Aïssatou Bailo Diallo","orcid":"0000-0002-9011-9069","position":10,"is_corresponding":false},{"id":1295503,"name":"Shih‐Ching Lo","orcid":"0000-0002-5187-0730","position":11,"is_corresponding":false},{"id":497316,"name":"Robin J. Kleiman","orcid":"0000-0002-9415-7433","position":12,"is_corresponding":false},{"id":612779,"name":"Christopher Henderson","orcid":"0000-0002-5291-5742","position":13,"is_corresponding":false},{"id":337685,"name":"Junghae Suh","orcid":"0000-0001-9280-9031","position":14,"is_corresponding":false},{"id":235551,"name":"Eric C. Griffith","orcid":"0000-0003-0428-3215","position":15,"is_corresponding":false},{"id":85691,"name":"Michael E. Greenberg","orcid":"0000-0003-1380-2160","position":16,"is_corresponding":false},{"id":235546,"name":"Siniša Hrvatin","orcid":"0000-0001-7303-4218","position":17,"is_corresponding":false},{"id":623215,"name":"M. Aurel Nagy","orcid":"0000-0003-4608-1152","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:04:42.082401Z","pmid":"39602276","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":[]}