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Fu, Haiyan; McCarty, Douglas M
Current opinion in virology, December 2016, 2016-12-00, 20161201, Volume: 21Journal Article
•Abundant vasculature could provide access to the CNS but is blocked by the BBB.•Disruption of BBB tight junctions allows paracellular transport of viral vectors.•Transient BBB disruption can be global or local.•Receptor-mediated transcytosis transports viral vectors across the intact BBB.•Directed evolution can greatly enhance vector transcytosis across BBB. The abundant vasculature of the CNS provides a compelling route of administration for the delivery of gene therapy vectors if the limitations imposed by the blood–brain-barrier (BBB) can be overcome. There are two general approaches to transporting viral vectors across the BBB: either by transient disruption of brain microvasculature endothelial tight junctions, or through the use of receptor-mediated transcytosis. Advances in BBB disruption have led to pre-clinical success for both global and localized gene delivery, while therapies based on receptor-mediated transcytosis have recently advanced to phase I clinical trials in humans. Both approaches show long term promise for treating a wide range of CNS diseases.
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