Adeno‐associated virus mediated gene therapy for vascular retinopathies

• Published in: Laboratory Techniques in Biochemistry and Molecular Biology Vol. 31; pp. 103 - 123
• Main Authors: Raisler, Brian J., Deng, Wen‐Tao, I. Berns, Kenneth, Hauswirth, William W.
• Format: Book Chapter
• Language: English
• Published: Elsevier Science & Technology 2005
• ISBN: 0444519491; 9780444519498
• ISSN: 0075-7535; 2589-2789
• DOI: 10.1016/S0075-7535(05)31005-9

The use of gene based therapy for the treatment of ocular neovascular disease offers advantages over conventional methods. By using a viral vector with a selective promoter to express the antiangiogenic protein or factor locally, expression can be limited to a specific cell type or subset of cell types within the retina. This reduces the safety concerns relative to systemic administration of antiangiogenic agents. Delivery of the vector to discreet compartments within the eye by sub-retinal or intravitreous injection may allow additional control of expression to only those local vessels that are affected. Choice of the appropriate viral vector for delivery of the therapeutic gene allows modulation of the duration of expression. Adeno-associated viral vectors appear to provide extended, perhaps even life-long, expression of therapeutic proteins within the eye. Several alternative viralvectored approaches have been reported. An adenoassociated viral vector (AAV) encoding the soluble vascular endothelial growth factor receptor 1, sFlt-1, shows promise for long-term inhibition of two types of ocular neovascularization. Another gene-based approach to treating neovascular disease involves the virally mediated intraocular expression of antiangiogenic agents. The chapter demonstrates that recombinant AAV vectors incorporating a CBA promoter are capable of producing sustained therapeutic levels of pigment epithelium derived factor (PEDF) and Kringle domains 1 through 3 of angiostatin (K1K3) in the mouse eye.