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S. Naylor, K. Binley, O. Kan, S. Iqball, S. Sims, A. Jun, P. Gouras, R. Allikmets, P. Campochiaro; The Development of EIAV-Based Lentiviral Gene Therapies for Neovascular AMD and Other Ocular Diseases. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1686.
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We have evaluated the potential of minimal Equine Infectious Anemia Virus (EIAV) based lentiviral vectors for ocular gene therapy of disorders that require efficient and sustained gene expression.Methods &
Following subretinal delivery EIAV vectors predominantly express within the retinal pigment epithelial cells (RPE) and to lesser extent in photoreceptors.The location of the RPE cells in the retina makes them an ideal platform for the production of secreted factors. For example we are developing RetinoStat® for clinical application in patients with neovascular AMD. RetinoStat is an EIAV vector expressing endostatin and angiostatin from an RPE-specific promoter. Proof of concept data will be presented from a series of studies in the laser-induced mouse model of choroidal neovascularisation (CNV).In contrast Stargardt disease (STGD) is a macular dystrophy caused by a mutation in the photoreceptor ATP binding transporter gene (ABCR) resulting in accumulation of the toxic lipofuscin pigment A2E. This leads to degeneration of RPE and photoreceptor cells. In this scenario we have developed EIAV vectors in combination with photoreceptor specific Rho promoter to deliver the wild type ABCR gene to photoreceptors in the Abca4-/- (knock-out) murine model of STGD. This resulted in a significant reduction (for the duration of the 4 month study) in A2E accumulation and thus shows promise for addressing this disease in the clinical setting.In addition to retinal cells we have shown that EIAV vectors can efficiently transduce corneal endothelial cells both in vivo following vector delivery to the anterior chamber in the mouse and in vitro in primary human corneal cells. This suggests that EIAV vectors could be developed to treat, corneal disorders such as Fuchs' Dystrophy and Keratoconus,
In conclusion, we will present data that indicate that EIAV-based vectors are an ideal choice for the development of long term therapies for a range of chronic ocular disorders.
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