{"doi":"10.1016/j.ymthe.2024.11.023","title":"CRISPR targeting of mmu-miR-21a through a single adeno-associated virus vector prolongs survival of glioblastoma-bearing mice","abstract":"Glioblastoma (GB), the most aggressive tumor of the central nervous system (CNS), has poor patient outcomes with limited effective treatments available. MicroRNA-21 (miR-21(a)) is a known oncogene, abundantly expressed in many cancer types. miR-21(a) promotes GB progression, and lack of miR-21(a) reduces the tumorigenic potential. Here, we propose a single adeno-associated virus (AAV) vector strategy targeting mmu-miR-21a using the Staphylococcus aureus Cas9 ortholog (SaCas9) guided by a single-guide RNA (sgRNA). Our results demonstrate that AAV8 is a well-suited AAV serotype to express SaCas9-KKH/sgRNA at the tumor site in an orthotopic GB model. The SaCas9-KKH induced a genomic deletion, resulting in lowered mmu-miR-21a levels in the brain, leading to reduced tumor growth and improved overall survival. In this study, we demonstrated that disruption of genomic mmu-miR-21a with a single AAV vector influenced glioma development, resulting in beneficial anti-tumor outcomes in GB-bearing mice.","journal":"Molecular Therapy","year":2024,"id":443695,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":1091988,"name":"Anne B. Vrijmoet","orcid":null,"position":1,"is_corresponding":false},{"id":1258873,"name":"Isabelle W Jetten","orcid":null,"position":2,"is_corresponding":false},{"id":731670,"name":"David Rufino‐Ramos","orcid":"0000-0002-5125-9667","position":3,"is_corresponding":false},{"id":1258874,"name":"Alexandra J E M de Reus","orcid":null,"position":4,"is_corresponding":false},{"id":2732,"name":"Koen Breyne","orcid":"0000-0002-0713-2407","position":5,"is_corresponding":false},{"id":44843,"name":"Benjamin P. Kleinstiver","orcid":"0000-0002-5469-0655","position":6,"is_corresponding":false},{"id":271598,"name":"Casey A. Maguire","orcid":"0000-0001-8681-5179","position":7,"is_corresponding":false},{"id":266752,"name":"Marike L. D. Broekman","orcid":"0000-0003-2205-5179","position":8,"is_corresponding":false},{"id":166012,"name":"XANDRA O. BREAKEFIELD","orcid":null,"position":9,"is_corresponding":false},{"id":266744,"name":"Erik R. Abels","orcid":"0000-0003-0146-3501","position":10,"is_corresponding":false},{"id":294638,"name":"Lisa Nieland","orcid":"0000-0002-4396-8252","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39563028","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":[]}