Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.
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.
Foust
Kevin D
KD
Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, Ohio 43205, USA.
Nurre
Emily
E
Montgomery
Chrystal L
CL
Hernandez
Anna
A
Chan
Curtis M
CM
Kaspar
Brian K
BK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics*; D005727:Ganglia, Spinal / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D019076:Transgenes
D049452:Green Fluorescent Proteins