Noninvasive targeted gene delivery into the brain using microbubble-facilitated focused ultrasound
Journal
PLoS ONE
Journal Volume
8
Journal Issue
2
Pages
e57682
Date Issued
2013
Author(s)
P-H Hsu
K-C Wei
C-Y Huang
C-J Wen
T-C Yen
C-L Liu
Y-T Lin
J-C Chen
C-R Shen
H-L Liu
P-H Hsu
K-C Wei
C-Y Huang
C-J Wen
T-C Yen
C-L Liu
Y-T Lin
J-C Chen
C-R Shen
H-L Liu
Abstract
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 the local, targeted delivery of rAAV vectors into the brains of mice by noninvasive, reversible, microbubble-facilitated focused ultrasound (FUS), resulting in BBB opening that can be monitored and controlled by magnetic resonance imaging (MRI). Using this method, we found that IV-administered AAV2-GFP (green fluorescence protein) with a low viral vector titer (1×10(9) vg/g) can successfully penetrate the BBB-opened brain regions to express GFP. We show that MRI monitoring of BBB-opening could serve as an indicator of the scale and distribution of AAV transduction. Transduction peaked at 3 weeks and neurons and astrocytes were affected. This novel, noninvasive delivery approach could significantly broaden the application of AAV-viral-vector-based genes for treatment of CNS diseases.
SDGs
Type
journal article