Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Kevin D. Foust,Emily Nurre,Emily Nurre,Chrystal L. Montgomery,Anna Hernandez,Curtis M Chan,Brian K. Kaspar,Brian K. Kaspar +7 more
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TLDR
It is shown that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS) and may enable the development of gene therapies for a range of neurodegenerative diseases.Abstract:
Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.read more
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References
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Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial.
Michael G. Kaplitt,Andrew Feigin,Andrew Feigin,Chengke Tang,Helen L. Fitzsimons,Paul J. Mattis,P. Lawlor,Ross J. Bland,Deborah Young,Kristin Strybing,David Eidelberg,David Eidelberg,Matthew J. During,Matthew J. During +13 more
TL;DR: AAV-GAD gene therapy of the subthalamic nucleus is safe and well tolerated by patients with advanced Parkinson's disease, suggesting that in-vivo gene therapy in the adult brain might be safe for various neurodegenerative diseases.
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Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues
Guangping Gao,Luk H. Vandenberghe,Mauricio R. Alvira,You Lu,Roberto Calcedo,Xiangyang Zhou,James M. Wilson +6 more
TL;DR: The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus as mentioned in this paper, although analyses of viruses and viral sequences from clinical samples are extremely limited.
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