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Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors
Journal article   Peer reviewed

Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors

Andrew J Lotery, Todd A Derksen, Stephen R Russell, Robert F Mullins, Sybille Sauter, Louisa M Affatigato, Edwin M Stone and Beverly L Davidson
Human gene therapy, Vol.13(6), pp.689-696
04/10/2002
DOI: 10.1089/104303402317322258
PMID: 11936968

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Abstract

We hypothesize that recombinant feline immunodeficiency viral (rFIV) vectors may be useful for gene transfer to the nonhuman primate retina. We performed vitrectomies and subretinal injections in the right eyes of 11 cynomolgus monkeys. Vesicular stomatitis virus glycoprotein-pseudotyped rFIV that expressed the Escherichia coli beta-galactosidase gene was injected into eight eyes. Sham vehicle or lactose buffer injections were also performed in two of these eight study eyes. rFIV pseudotyped with an amphotropic envelope was used in two eyes, and in one animal injections of lactose buffer only were given. After surgery the animals were clinically evaluated by retinal photography and electroretinography. beta-Galactosidase expression was evaluated, at a final end point, in histological sections. We found photoreceptor and Müller cells to have the greatest transgene expression. Focal inflammatory responses localized to the injection site were seen histologically in all eyes. No difference in transduction efficiency was seen between injections near the macula and more peripheral injections. Visual function as assessed by electroretinography was not significantly affected by vector or vehicle injections. We conclude that rFIV vectors administered beneath the retina can transduce a variety of retinal cells in the nonhuman primate retina. rFIV vectors have therapeutic potential and could be exploited to develop gene therapy for the human eye.
Gene Transfer Techniques Gene Expression Viral Envelope Proteins - genetics Humans Macaca fascicularis Retina Genetic Vectors - genetics Animals Recombination, Genetic Immunodeficiency Virus, Feline - genetics Primates Genetic Vectors - physiology Immunodeficiency Virus, Feline - physiology Membrane Glycoproteins beta-Galactosidase - genetics Genes, Reporter

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