Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes

• Published in: Nature biotechnology Vol. 27; no. 1; pp. 59 - 65
• Main Authors: Kaspar, Brian K, Foust, Kevin D, Nurre, Emily, Montgomery, Chrystal L, Hernandez, Anna, Chan, Curtis M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2009; Nature Publishing Group
• Subjects: Adeno-associated virus; Agriculture; Animals; Astrocytes - metabolism; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cellular biology; Central nervous system; Degeneration; Dependovirus - genetics; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; Gene therapy; Gene Transfer Techniques; Genetic aspects; Genetic Vectors; Green Fluorescent Proteins - metabolism; Health. Pharmaceutical industry; Hippocampus - metabolism; In Situ Hybridization; Industrial applications and implications. Economical aspects; Injection; Life Sciences; Mice; Mice, Inbred C57BL; Muscular Atrophy, Spinal - metabolism; Neocortex - metabolism; Nervous system; Neurons; Neurons - metabolism; Rodents; Transgenes; Virology; United States; Human; Adenoviridae; Intravenous administration; Targeting; Rodentia; Central nervous system; Astrocyte; Encephalon; Virus; Associated virus; Vertebrata; Mammalia; Neuron; Newborn; Mouse; Adult; Gene therapy; Vector
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.1515

Foust et al . describe a viral vector that crosses the blood-brain barrier, providing a non-invasive method for delivering therapeutic genes to the central nervous system. A single intravascular injection of AAV9 results in widespread transduction of astrocytes in adult mice and of astrocytes and neurons in neonatal mice. 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.