Therapeutic Genome Editing of Gliomas via Focused Ultrasound-Mediated Ribonucleoprotein Delivery

Introduction: Efflux pumps (e.g. P-glycoprotein (P-gp)) are hallmarks of the blood-brain barrier that significantly hinder chemotherapy delivery to glioblastoma (GBM) (1). Pharmacological P-gp inhibitors have limited utility because blocking P-gp in healthy tissues yields heightened chemotherapy toxicity. A non-invasive and spatially-targeted strategy to block P-gp would have substantial clinical impact. Here, we developed a focused ultrasound (FUS)-targeted delivery approach for ribonucleoprotein (RNP) CRISPR/Cas9-based genomic deletion of P-gp in GBM that augments the efficacy of chemotherapy.