Noninvasive and Targeted Gene Delivery into the Brain Using Microbubble-Facilitated Focused Ultrasound

摘要: Recombinant adeno-associated viral (rAAV) vectors are potentially powerful tools for gene therapy of CNS diseases, but their penetration into brain parenchyma is severely limited by the blood-brain barrier (BBB) and current delivery relies on invasive stereotactic injection. Here we evaluate local, targeted rAAV brains mice noninvasive, reversible, microbubble-facilitated focused ultrasound (FUS), resulting in BBB opening that can be monitored controlled magnetic resonance imaging (MRI). Using this method, found IV-administered AAV2-GFP (green fluorescence protein) with a low vector titer (1×109 vg/g) successfully penetrate BBB-opened regions to express GFP. We show MRI monitoring BBB-opening could serve as an indicator scale distribution AAV transduction. Transduction peaked at 3 weeks neurons astrocytes were affected. This novel, noninvasive approach significantly broaden application AAV-viral-vector-based genes treatment diseases.