MRI-Guided Focused Ultrasound for Targeted Delivery of rAAV to the Brain.
Animals
Biological Transport
Blood-Brain Barrier
/ metabolism
Brain
/ diagnostic imaging
Dependovirus
/ genetics
Gene Expression
Gene Transfer Techniques
Genes, Reporter
Genetic Vectors
/ administration & dosage
Magnetic Resonance Imaging
/ methods
Mice
Neuronavigation
/ methods
Permeability
/ radiation effects
Rats
Transgenes
Ultrasonography
/ methods
Adeno-associated virus
Blood-brain barrier
Focused ultrasound
Gene therapy
Viral vector delivery
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2019
2019
Historique:
entrez:
21
2
2019
pubmed:
21
2
2019
medline:
17
7
2019
Statut:
ppublish
Résumé
Recombinant adeno-associated viral (rAAV) vectors are a promising tool for therapeutic gene delivery to the brain. However, the delivery of rAAVs across the blood-brain barrier (BBB) and entry into the brain remains a major challenge for rAAV-based gene therapy. To circumvent this limitation, transcranial MRI-guided focused ultrasound (MRIgFUS) combined with intravenously injected microbubbles has been used to transiently and reversibly increase BBB permeability in targeted brain regions. Systemic administration of rAAVs at the time of sonication with focused ultrasound (FUS) facilitates the passage of rAAVs through the BBB and into the brain parenchyma. We and others have demonstrated that FUS-mediated rAAV delivery to the brain results in efficient transduction and transgene expression in vivo. Using this approach, the dose of intravenously injected rAAV variants that can cross the BBB can be reduced by 100 times, achieving significant transgene expression in the brain parenchyma with reduced peripheral transduction. Moreover, this strategy can be used to deliver rAAV variants that do not cross the BBB from the blood to selected brain regions. Here, we provide a detailed protocol for FUS-induced BBB permeability for targeted rAAV delivery to the brain of adult mice and rats.
Identifiants
pubmed: 30783974
doi: 10.1007/978-1-4939-9139-6_10
pmc: PMC6546162
mid: NIHMS1020877
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
177-197Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB003268
Pays : United States
Organisme : CIHR
ID : FRN137064
Pays : Canada
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