PMID- 24572783
OWN - NLM
STAT- MEDLINE
DCOM- 20150110
LR  - 20211021
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 21
IP  - 5
DP  - 2014 May
TI  - Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron 
      transduction in the whole central nervous system of cats.
PG  - 522-8
LID - 10.1038/gt.2014.16 [doi]
AB  - 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.
FAU - Bucher, T
AU  - Bucher T
AD  - Laboratoire de Therapie Genique, INSERM UMR U1089, Institut de Recherche 
      Therapeutique 1, Universite de Nantes, Nantes Cedex 01, France.
FAU - Dubreil, L
AU  - Dubreil L
AD  - 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.
FAU - Colle, M-A
AU  - Colle MA
AD  - 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.
FAU - Maquigneau, M
AU  - Maquigneau M
AD  - Laboratoire de Therapie Genique, INSERM UMR U1089, Institut de Recherche 
      Therapeutique 1, Universite de Nantes, Nantes Cedex 01, France.
FAU - Deniaud, J
AU  - Deniaud J
AD  - 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.
FAU - Ledevin, M
AU  - Ledevin M
AD  - 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.
FAU - Moullier, P
AU  - Moullier P
AD  - 1] Laboratoire de Therapie Genique, INSERM UMR U1089, Institut de Recherche 
      Therapeutique 1, Universite de Nantes, Nantes Cedex 01, France [2] Department of 
      Molecular Genetics and Microbiology, College of Medicine, University of Florida, 
      Gainesville, FL, USA.
FAU - Joussemet, B
AU  - Joussemet B
AD  - Laboratoire de Therapie Genique, INSERM UMR U1089, Institut de Recherche 
      Therapeutique 1, Universite de Nantes, Nantes Cedex 01, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140227
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Brain/cytology/*virology
MH  - Cats
MH  - Cerebrospinal Fluid/virology
MH  - Dependovirus/*genetics
MH  - Genetic Therapy
MH  - Genetic Vectors/*genetics
MH  - Green Fluorescent Proteins/administration & dosage/genetics
MH  - Motor Neurons/cytology/*virology
MH  - Neuroglia/cytology
MH  - Neurons/cytology
MH  - Oligodendroglia/cytology/*virology
MH  - Spinal Cord/cytology/virology
MH  - Transduction, Genetic
PMC - PMC4015314
EDAT- 2014/02/28 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/02/28 06:00
PHST- 2013/08/13 00:00 [received]
PHST- 2013/12/12 00:00 [revised]
PHST- 2014/01/07 00:00 [accepted]
PHST- 2014/02/28 06:00 [entrez]
PHST- 2014/02/28 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - gt201416 [pii]
AID - 10.1038/gt.2014.16 [doi]
PST - ppublish
SO  - Gene Ther. 2014 May;21(5):522-8. doi: 10.1038/gt.2014.16. Epub 2014 Feb 27.