title: Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron transduction in the whole central nervous system of cats.
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.
authors.affiliation: Laboratoire de Thérapie Génique, INSERM UMR U1089, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes Cedex 01, France.
authors.forename: T
authors.initials: T
authors.lastname: Bucher
authors.affiliation: 1] INRA UMR U703, Animal Pathophysiology and Biotherapy for Muscle and CNS Diseases, Nantes, France [2] Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (Oniris), LUNAM University, Nantes Cedex 03, France.
authors.forename: L
authors.initials: L
authors.lastname: Dubreil
authors.affiliation: 1] INRA UMR U703, Animal Pathophysiology and Biotherapy for Muscle and CNS Diseases, Nantes, France [2] Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (Oniris), LUNAM University, Nantes Cedex 03, France.
authors.forename: M-A
authors.initials: MA
authors.lastname: Colle
authors.affiliation: Laboratoire de Thérapie Génique, INSERM UMR U1089, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes Cedex 01, France.
authors.forename: M
authors.initials: M
authors.lastname: Maquigneau
authors.affiliation: 1] INRA UMR U703, Animal Pathophysiology and Biotherapy for Muscle and CNS Diseases, Nantes, France [2] Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (Oniris), LUNAM University, Nantes Cedex 03, France.
authors.forename: J
authors.initials: J
authors.lastname: Deniaud
authors.affiliation: 1] INRA UMR U703, Animal Pathophysiology and Biotherapy for Muscle and CNS Diseases, Nantes, France [2] Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (Oniris), LUNAM University, Nantes Cedex 03, France.
authors.forename: M
authors.initials: M
authors.lastname: Ledevin
authors.affiliation: 1] Laboratoire de Thérapie Génique, INSERM UMR U1089, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes Cedex 01, France [2] Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Moullier
authors.affiliation: Laboratoire de Thérapie Génique, INSERM UMR U1089, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes Cedex 01, France.
authors.forename: B
authors.initials: B
authors.lastname: Joussemet
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000821:virology*; D002415:Cats; D002555:Cerebrospinal Fluid / Q000821:virology; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology / Q000821:virology*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D009836:Oligodendroglia / Q000166:cytology / Q000821:virology*; D013116:Spinal Cord / Q000166:cytology / Q000821:virology; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins