Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron transduction in the whole central nervous system of cats

Gene Ther. 2014 May;21(5):522-8. doi: 10.1038/gt.2014.16. Epub 2014 Feb 27.

Abstract

Systemic and intracerebrospinal fluid delivery of adeno-associated virus serotype 9 (AAV9) has been shown to achieve widespread gene delivery to the central nervous system (CNS). However, after systemic injection, the neurotropism of the vector has been reported to vary according to age at injection, with greater neuronal transduction in newborns and preferential glial cell tropism in adults. This difference has not yet been reported after cerebrospinal fluid (CSF) delivery. The present study analyzed both neuronal and glial cell transduction in the CNS of cats according to age of AAV9 CSF injection. In both newborns and young cats, administration of AAV9-GFP in the cisterna magna resulted in high levels of motor neurons (MNs) transduction from the cervical (84±5%) to the lumbar (99±1%) spinal cord, demonstrating that the remarkable tropism of AAV9 for MNs is not affected by age at CSF delivery. Surprisingly, numerous oligodendrocytes were also transduced in the brain and in the spinal cord white matter of young cats, but not of neonates, indicating that (i) age of CSF delivery influences the tropism of AAV9 for glial cells and (ii) AAV9 intracisternal delivery could be relevant for both the treatment of MN and demyelinating disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Brain / cytology
  • Brain / virology*
  • Cats
  • Cerebrospinal Fluid / virology
  • Dependovirus / genetics*
  • Genetic Therapy
  • Genetic Vectors / genetics*
  • Green Fluorescent Proteins / administration & dosage
  • Green Fluorescent Proteins / genetics
  • Motor Neurons / cytology
  • Motor Neurons / virology*
  • Neuroglia / cytology
  • Neurons / cytology
  • Oligodendroglia / cytology
  • Oligodendroglia / virology*
  • Spinal Cord / cytology
  • Spinal Cord / virology
  • Transduction, Genetic

Substances

  • Green Fluorescent Proteins