title: Neonatal systemic delivery of scAAV9 in rodents and large animals results in gene transfer to RPE cells in the retina.
abstract: Systemic delivery of recombinant adeno-associated virus (rAAV) vectors has recently been shown to cross the blood brain barrier in rodents and large animals and to efficiently target cells of the central nervous system. Such approach could be particularly interesting to treat lysosomal storage diseases or neurodegenerative disorders characterized by multiple organs injuries especially neuronal and retinal dysfunctions. However, the ability of rAAV vector to cross the blood retina barrier and to transduce retinal cells after systemic injection has not been precisely determined. In this study, gene transfer was investigated in the retina of neonatal and adult rats after intravenous injection of self-complementary (sc) rAAV serotype 1, 5, 6, 8, and 9 carrying a CMV-driven green fluorescent protein (GFP), by fluorescence fundus photography and histological examination. Neonatal rats injected with scAAV2/9 vector displayed the strongest GFP expression in the retina, within the retinal pigment epithelium (RPE) cells. Retinal tropism of scAAV2/9 vector was further assessed after systemic delivery in large animal models, i.e., dogs and cats. Interestingly, efficient gene transfer was observed in the RPE cells of these two large animal models following neonatal intravenous injection of the vector. The ability of scAAV2/9 to transduce simultaneously neurons in the central nervous system, and RPE cells in the retina, after neonatal systemic delivery, makes this approach potentially interesting for the treatment of infantile neurodegenerative diseases characterized by both neuronal and retinal damages.
authors: INSERM UMR U649, Institut de Recherche Thérapeutique 1, Université de Nantes, 8 quai Moncousu, 44007 Nantes Cedex 01, France. beatrice.joussemet@univ-nantes.fr
authors: Béatrice
authors: B
authors: Joussemet
authors: Brahim
authors: B
authors: Belbellaa
authors: Alexandra
authors: A
authors: Mendes-Madeira
authors: Thomas
authors: T
authors: Bucher
authors: Delphine
authors: D
authors: Briot-Nivard
authors: Laurence
authors: L
authors: Dubreil
authors: Marie-Anne
authors: MA
authors: Colle
authors: Yan
authors: Y
authors: Cherel
authors: Philippe
authors: P
authors: Moullier
authors: Fabienne
authors: F
authors: Rolling
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002415:Cats; D018076:DNA, Complementary; D000229:Dependovirus / Q000235:genetics*; D004285:Dogs; D005260:Female; D005451:Fluorescein Angiography; D015870:Gene Expression / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000276:immunology; D007275:Injections, Intravenous; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D019076:Transgenes
chemical_list: D018076:DNA, Complementary; D049452:Green Fluorescent Proteins