Brain-Targeted Intranasal Delivery of Protein-Based Gene Therapy for Treatment of Ischemic Stroke

This study presents a novel approach for treating ischemic stroke using a protein-based CRISPR/dCas9 system delivered intranasally. The system targets the neuroprotective gene <i>Sirt1</i> and is encapsulated in calcium phosphate nanoparticles to enhance stability and prevent degradation. These nanoparticles are conjugated with β-hydroxybutyrates to facilitate transfer into the brain via nasal epithelial cells. In a mouse model, this method effectively upregulated <i>Sirt1</i>, reduced cerebral edema, and increased survival rates after stroke, with no significant toxicity observed. The findings suggest that this delivery system could be a promising therapy for acute ischemic stroke.