Neonatal systemic delivery of scAAV9 in rodents and large animals results in gene transfer to RPE cells in the retina.
Exp Eye Res
; 93(4): 491-502, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21723863
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retina
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Expresión Génica
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Técnicas de Transferencia de Gen
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Dependovirus
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Proteínas Fluorescentes Verdes
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Epitelio Pigmentado de la Retina
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Vectores Genéticos
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
Exp Eye Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Francia