{"doi":"10.1016/j.omtn.2025.102466","title":"Non-invasive detection of allele-specific CRISPR-SaCas9-KKH disruption of TOR1A DYT1 allele in a xenograft mouse model","abstract":"DYT1 dystonia is a neurological movement disorder characterized by a dominant 3-base pair deletion (ΔGAG) in the TOR1A gene. This study demonstrates a gene-editing approach that selectively targets the ΔGAG mutation in the TOR1A DYT1 allele while safeguarding the wild-type (WT) TOR1A allele. We optimized an adeno-associated virus (AAV) vector-compatible variant of the Staphylococcus aureus Cas9 nuclease ortholog (SaCas9-KKH) in DYT1 patient-derived human neuronal progenitor cells (hNPCs). On-target editing of the TOR1A DYT1 allele was confirmed at the genomic level from brain tissue in a xenograft mouse model. To avoid brain biopsy for demonstrating TOR1A DYT1 editing, we developed a non-invasive monitoring method using extracellular RNA (exRNA). TOR1A exRNA was retrieved from the extracellular vesicle (EV) secretions of hNPCs and plasma samples, indicating whether the donor was a TOR1A DYT1 carrier. This technique enabled us to assess AAV-mediated disruption of the TOR1A DYT1 allele in the brains of mice using blood samples.","journal":"Molecular Therapy — Nucleic Acids","year":2025,"id":551372,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":1368569,"name":"Dawn Madison Frederick","orcid":null,"position":1,"is_corresponding":false},{"id":342086,"name":"Nutan Sharma","orcid":"0000-0002-4445-7374","position":2,"is_corresponding":false},{"id":1439923,"name":"Edwina Abou Haidar","orcid":"0000-0002-7866-8030","position":3,"is_corresponding":false},{"id":1298398,"name":"Tianhe Xiao","orcid":null,"position":4,"is_corresponding":false},{"id":1447518,"name":"Justin Seungkyu Han","orcid":null,"position":5,"is_corresponding":false},{"id":814054,"name":"Mohammed Mahamdeh","orcid":"0000-0003-3985-6992","position":6,"is_corresponding":false},{"id":451680,"name":"Roy J. Soberman","orcid":"0000-0002-2817-0517","position":7,"is_corresponding":false},{"id":731670,"name":"David Rufino‐Ramos","orcid":"0000-0002-5125-9667","position":8,"is_corresponding":false},{"id":44843,"name":"Benjamin P. Kleinstiver","orcid":"0000-0002-5469-0655","position":9,"is_corresponding":false},{"id":350763,"name":"Hyder A. Jinnah","orcid":"0000-0003-1531-3969","position":10,"is_corresponding":false},{"id":1367985,"name":"Christine A. Vaine","orcid":"0000-0003-2645-8223","position":11,"is_corresponding":false},{"id":441305,"name":"D. Cristopher Bragg","orcid":"0000-0003-3203-6262","position":12,"is_corresponding":false},{"id":2732,"name":"Koen Breyne","orcid":"0000-0002-0713-2407","position":13,"is_corresponding":false},{"id":1367984,"name":"Katia Maalouf","orcid":"0000-0002-0881-7328","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:54:25.065895Z","pmid":"40114706","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":[]}