title: Subretinal delivery of recombinant AAV serotype 8 vector in dogs results in gene transfer to neurons in the brain.
abstract: Recombinant adeno-associated virus (rAAV) vectors are among the most efficient gene delivery vehicles for gene transfer to the retina. This study evaluates the behavior of the rAAV8 serotype vector with regard to intraocular delivery in rats and dogs. Subretinal delivery of an AAV2/8.gfp vector results in efficient gene transfer in the retinal pigment epithelium (RPE), the photoreceptors and, surprisingly, in the cells of the inner nuclear layer as well as in ganglion cells. Most importantly, in dogs, gene transfer also occurred distal to the injection site in neurons of the lateral geniculate nucleus of the brain. Because green fluorescent protein (GFP) was detected along the visual pathway within the brain, we analyzed total DNA extracted from various brain slices using PCR. Vector sequences were detected in many parts of the brain, but chiefly in the contralateral hemisphere.
authors.affiliation: INSERM U649, CHU Hotel-Dieu, Nantes, France.
authors.forename: Knut
authors.initials: K
authors.lastname: Stieger
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Colle
authors.forename: Laurence
authors.initials: L
authors.lastname: Dubreil
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mendes-Madeira
authors.forename: Michel
authors.initials: M
authors.lastname: Weber
authors.forename: Guylène
authors.initials: G
authors.lastname: Le Meur
authors.forename: Jack Yves
authors.initials: JY
authors.lastname: Deschamps
authors.forename: Nathalie
authors.initials: N
authors.lastname: Provost
authors.forename: Delphine
authors.initials: D
authors.lastname: Nivard
authors.forename: Yan
authors.initials: Y
authors.lastname: Cherel
authors.forename: Philippe
authors.initials: P
authors.lastname: Moullier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Rolling
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D000229:Dependovirus / Q000378:metabolism*; D004285:Dogs; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism*
chemical_list: D049452:Green Fluorescent Proteins