Intravascular AAV9 preferentially targets neonatal-neurons and adult-astrocytes in CNS
By K. Foust, Emily Nurre, Chrystal L. Montgomery, Anna Hernandez, Curtis M. Chan, B. Kaspar. Nature Biotechnology, 2008
1,350 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e421bbe7eac1c5841366168490b835420ef55818
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Citations in the corpus
- Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis (2014, neutral): “However, targeting NF-kB is complicated due to its diverse functions in different cell types in the CNS and periphery.”
- Current Clinical Applications of In Vivo Gene Therapy with AAVs (2020, background): “It was confirmed in SMA murine models that systemically delivered selfcomplementary AAV9 (scAAV9) crossed the blood brain barrier and achieved high levels of neuronal transduction.(9,10) Preclinical studies, delivering scAAV9-SMN to SMA pups, demonstrated positive effects on survival, growth, and ne”
- Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons (2011, background): “Recently, novel vectors have been shown to efficiently target astrocytes of adult brain and spinal cor”
- Current Strategies for Brain Drug Delivery (2018, background): “was the first to demonstrate extensive transduction of neonatal neurons and adult astrocytes in mice by intravenous administration of AAV9 at a high dose of 2 x 104 vg/kg [28].”