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

Po Hung Hsu, Kuo Chen Wei, Chiung Yin Huang, Chih Jen Wen, Tzu Chen Yen, Chao Lin Liu, Ya Tin Lin, Jin Chung Chen, Chia Rui Shen, Hao Li Liu

研究成果: 雜誌貢獻文章同行評審

103 引文 斯高帕斯(Scopus)

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 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 (1×109 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.
原文英語
文章編號e57682
期刊PLoS ONE
8
發行號2
DOIs
出版狀態已發佈 - 2月 27 2013
對外發佈

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)
  • 多學科

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