title: Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates.
abstract: We report on the long-term safety of AAV2.sFlt-1 (a recombinant adeno-associated virus serotype 2 carrying the soluble form of the Flt-1 receptor) injection into the subretinal space of non-human primates. Levels of sFlt-1 protein were significantly higher (P<0.05) in the vitreous of four out of five AAV2.sFlt-1-injected eyes. There was no evidence of damage to the eyes of animals that received subretinal injections of AAV2.sFlt-1; ocular examination showed no anterior chamber flare, normal fundus and electroretinography responses equivalent to those observed before treatment. Notably, immunological analysis demonstrated that gene therapy involving subretinal injection of AAV2.sFlt-1 does not elicit cell-mediated immunity. Biodistribution analysis showed that AAV2.sFlt-1 could be detected only in the eye and not in the other organs tested. These data indicate that gene therapy with subretinal AAV2.sFlt-1 is safe and well tolerated, and therefore promising for the long-term treatment of neovascular diseases of the eye.
authors.affiliation: Centre for Ophthalmology and Visual Sciences, Department of Molecular Ophthalmology, The University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: C-M
authors.initials: CM
authors.lastname: Lai
authors.forename: M J
authors.initials: MJ
authors.lastname: Estcourt
authors.forename: R P
authors.initials: RP
authors.lastname: Himbeck
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Yew-San Yeo
authors.forename: C
authors.initials: C
authors.lastname: Luu
authors.forename: B K
authors.initials: BK
authors.lastname: Loh
authors.forename: M W
authors.initials: MW
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Barathi
authors.forename: J
authors.initials: J
authors.lastname: Villano
authors.forename: C-L
authors.initials: CL
authors.lastname: Ang
authors.forename: R G
authors.initials: RG
authors.lastname: van der Most
authors.forename: I J
authors.initials: IJ
authors.lastname: Constable
authors.forename: D
authors.initials: D
authors.lastname: Dismuke
authors.forename: R J
authors.initials: RJ
authors.lastname: Samulski
authors.forename: M A
authors.initials: MA
authors.lastname: Degli-Esposti
authors.forename: E P
authors.initials: EP
authors.lastname: Rakoczy
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D008252:Macaca fascicularis; D012160:Retina / Q000276:immunology / Q000378:metabolism; D015861:Retinal Neovascularization / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1