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Plos One : Noninvasive and Targeted Gene Delivery Into the Brain Using Microbubble-facilitated Focused Ultrasound, Volume 8

By Ulasov, Ilya

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Book Id: WPLBN0003963941
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Noninvasive and Targeted Gene Delivery Into the Brain Using Microbubble-facilitated Focused Ultrasound, Volume 8  
Author: Ulasov, Ilya
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Publication Date:
Publisher: Plos

Description : 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 (16109 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.


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