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CRISPR-SaCas9-KKH targeting of miR-21 through a single adeno-associated virus vector prolongs survival of GB-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) is a known oncogene, abundantly expressed in many cancer types. MiR-21 promotes glioblastoma progression, and lack of miR-21 reduces tumorigenic potential of tumor. Here, we propose a single adeno-associated virus (AAV) vector strategy targeting miR-21 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 glioblastoma model. The SaCas9-KKH induced a genomic deletion, resulting in lowered miR-21 levels in the brain, leading to reduced tumor growth and improved overall survival. In this study we demonstrated that a single AAV-mediated mir-21 disruption influences glioma development resulting in beneficial anti-tumor outcomes in GB-bearing mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE277282 | GEO | 2024/11/27

REPOSITORIES: GEO

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