Cited by 136Ultrasound and Hyperthermia ApplicationsVirus-based gene therapy researchBarrier Structure and Function Studies

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

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Hsu, Po-Hung, Wei, Kuo-Chen, Huang, Chiung-Yin, Wen, Chih-Jen, Yen, Tzu-Chen, Liu, Chao-Lin, Lin, Ya-Tin, Chen, Jin-Chung, Shen, Chia-Rui, Liu, Hao-Li·2013·PLoS ONE

DOI 10.1371/journal.pone.0057682PMC PMC3584045

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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.

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N Carty, 2010, Convection-enhanced delivery and systemic mannitol increase gene product distribution of AAV vectors 5, 8, and 9 and increase gene product in the adult mouse brain, J Neurosci Methods, 194, 144, 10.1016/j.jneumeth.2010.10.010 · DOI

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Authors: Hsu, P.-H., Wei, K.-C., Huang, C.-Y., Wen, C.-J., Yen, T.-C., Liu, C.-L., Lin, Y.-T., Chen, J.-C., Shen, C.-R., & Liu, H.-L.
Affiliations: Chang Gung University (TW)
Ming Chi University of Technology (TW)
Corresponding author: Shen, Chia-Rui
Liu, Hao-Li
ORCID: Hsu, Po-Hung
Wei, Kuo-Chen
Huang, Chiung-Yin
Yen, Tzu-Chen
Liu, Chao-Lin
Lin, Ya-Tin
Chen, Jin-Chung
Shen, Chia-Rui
Liu, Hao-Li
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2013-02-27
Volume: 8
Issue: 2
Pages: e57682
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0057682
PMC: PMC3584045
OpenAlex: W1969401867
Cited by: 136
References: 57
Citations by year: 2026: 5 · 2025: 8 · 2024: 9 · 2023: 4 · 2022: 12 · 2021: 20 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 3 · 2016: 9 · 2015: 14 · 2014: 13 · 2013: 2
FWCI: 6.99
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: National Science Council (100-2321-B-182-010)
Chang Gung Medical Foundation
Topics: Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: gene therapy, adeno-associated virus vectors, focused ultrasound, microbubbles, blood-brain barrier disruption, central nervous system disorders
MeSH terms: Dependovirus, Animals, Astrocytes, Blood-Brain Barrier, Brain, Contrast Media, Fluorescent Antibody Technique, Genetic Vectors, Magnetic Resonance Imaging, Male, Mice, Inbred ICR, Transduction, Genetic, Ultrasonics, Blotting, Western, Reproducibility of Results, Gene Transfer Techniques, Microbubbles, Green Fluorescent Proteins, Mice

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

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