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Graham Price, Jackie de Belin, Julie Loader, Michelle Kelleher, James Miskin, Georgina Ferrige, Marie Carlucci, Diana Angell-Manning, Stuart Naylor, Peter Widdowson; Biodistribution and Immunological Response of the Subretinally Injected Lentiviral-Vector StarGenTM in Rabbits and Macaques. Invest. Ophthalmol. Vis. Sci. 2011;52(14):482.
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© ARVO (1962-2015); The Authors (2016-present)
StarGenTM is a new lentiviral vector-based gene therapy for the treatment of Stargardt disease which is designed to express the normal ATP binding cassette transporter gene ABCA4 within the retina. The biodistribution and immunological response to StarGenTM was examined in GLP studies in both rabbits and non-human primates (NHPs) following subretinal administration.
StarGenTM was injected subretinally in the right eye only of both Dutch-belted pigmented rabbits, and in Rhesus macaques. Serum samples were collected periodically prior to and after dosing to evaluate antibody responses against components of the vector. Tear/eye exudates, plasma, urine and tissue samples were taken from both rabbits (Day 3, 1 week, 1 month and 3 months after dosing) and macaques (3 and 6 months) during the study to examine for vector presence using qPCR.
StarGenTM vector sequences were detected in the target retina/choroid and in the majority of scleral samples obtained from the rabbits. Rabbit vitreous samples were positive for vector for up to one month after which they remained negative. StarGenTM was not detected in the organs, including testes or ovaries, at any time point. No immune responses were identified to the transgene ABCA4, some antibody responses were detected principally to the envelope protein VSVG-2. However, there were no toxicities associated with this finding.
Subretinal delivery of StarGenTM vector in Dutch-belted rabbits and Rhesus macaques remains largely within the ocular compartment. The immunological response to components of the StarGenTM lentiviral product did not result in any long term toxicity issues.
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