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

Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors
Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors
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 ?-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. ?-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.
1043-0342
689-696
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Derksen, Todd A.
a941ccf5-1bad-4def-bd65-da8286ff5ea1
Russell, Stephen R.
f8f01d5a-13b7-4cbc-963d-8f48f4a2d6d0
Mullins, Robert F.
e9691938-809a-4b0f-b8fc-de8b181bf26f
Sauter, Sybille
93da134c-5076-4215-9721-0e010d419d8e
Affatigato, Louisa M.
dcb740c4-f0a1-41ab-ab3f-30d0fe76bc20
Stone, Edwin M.
f0ff92fa-f668-4fb5-943b-5e073bd0fd1f
Davidson, Beverly L.
b96b9763-cc02-4966-bb93-7c974d34733d
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Derksen, Todd A.
a941ccf5-1bad-4def-bd65-da8286ff5ea1
Russell, Stephen R.
f8f01d5a-13b7-4cbc-963d-8f48f4a2d6d0
Mullins, Robert F.
e9691938-809a-4b0f-b8fc-de8b181bf26f
Sauter, Sybille
93da134c-5076-4215-9721-0e010d419d8e
Affatigato, Louisa M.
dcb740c4-f0a1-41ab-ab3f-30d0fe76bc20
Stone, Edwin M.
f0ff92fa-f668-4fb5-943b-5e073bd0fd1f
Davidson, Beverly L.
b96b9763-cc02-4966-bb93-7c974d34733d

Lotery, Andrew J., Derksen, Todd A., Russell, Stephen R., Mullins, Robert F., Sauter, Sybille, Affatigato, Louisa M., Stone, Edwin M. and Davidson, Beverly L. (2002) Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors. Human Gene Therapy, 13 (6), 689-696. (doi:10.1089/104303402317322258).

Record type: Article

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 ?-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. ?-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.

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Published date: 10 April 2002

Identifiers

Local EPrints ID: 24839
URI: http://eprints.soton.ac.uk/id/eprint/24839
ISSN: 1043-0342
PURE UUID: 4b835c1f-1fee-4c44-97ab-dfe27e54179d
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 05 Apr 2006
Last modified: 16 Mar 2024 03:31

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Contributors

Author: Todd A. Derksen
Author: Stephen R. Russell
Author: Robert F. Mullins
Author: Sybille Sauter
Author: Louisa M. Affatigato
Author: Edwin M. Stone
Author: Beverly L. Davidson

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