2009 January | Kevin D. Foust, Emily Nurre, Chrystal L. Montgomery, Anna Hernandez, Curtis M. Chan, and Brian K. Kaspar
This study investigates the intravenous delivery of adeno-associated virus 9 (AAV9) to the central nervous system (CNS) in neonatal and adult mice, revealing distinct targeting patterns. In neonatal animals, AAV9 efficiently targets motor neurons in the spinal cord and astrocytes in the adult brain. In adult mice, AAV9 primarily targets astrocytes in the spinal cord and brain, suggesting a unique transduction property. The study demonstrates that AAV9 can cross the blood-brain barrier (BBB) in neonates but not in adults, highlighting the importance of developmental stage in viral entry. Intravenous delivery of AAV9 in neonates results in widespread transduction of motor neurons and astrocytes, while in adults, it primarily targets astrocytes. The study also shows that AAV9 can transduce astrocytes in the adult brain, which may be relevant for treating amyotrophic lateral sclerosis (ALS), where astrocytes are involved in disease progression. The findings suggest that AAV9 has potential as a therapeutic vector for neurodegenerative diseases such as spinal muscular atrophy (SMA) and ALS. The study highlights the importance of understanding the mechanisms of viral entry and transduction in the CNS for developing effective gene therapy strategies. The results indicate that AAV9 can efficiently deliver genes to widespread regions of the CNS, offering a promising approach for treating neurological disorders. The study also emphasizes the need for further research to understand the mechanisms of AAV9 transduction and to optimize its use in clinical settings.This study investigates the intravenous delivery of adeno-associated virus 9 (AAV9) to the central nervous system (CNS) in neonatal and adult mice, revealing distinct targeting patterns. In neonatal animals, AAV9 efficiently targets motor neurons in the spinal cord and astrocytes in the adult brain. In adult mice, AAV9 primarily targets astrocytes in the spinal cord and brain, suggesting a unique transduction property. The study demonstrates that AAV9 can cross the blood-brain barrier (BBB) in neonates but not in adults, highlighting the importance of developmental stage in viral entry. Intravenous delivery of AAV9 in neonates results in widespread transduction of motor neurons and astrocytes, while in adults, it primarily targets astrocytes. The study also shows that AAV9 can transduce astrocytes in the adult brain, which may be relevant for treating amyotrophic lateral sclerosis (ALS), where astrocytes are involved in disease progression. The findings suggest that AAV9 has potential as a therapeutic vector for neurodegenerative diseases such as spinal muscular atrophy (SMA) and ALS. The study highlights the importance of understanding the mechanisms of viral entry and transduction in the CNS for developing effective gene therapy strategies. The results indicate that AAV9 can efficiently deliver genes to widespread regions of the CNS, offering a promising approach for treating neurological disorders. The study also emphasizes the need for further research to understand the mechanisms of AAV9 transduction and to optimize its use in clinical settings.