The treatment of inherited dystrophies and neovascular disorders of the retina by rAAV-mediated gene therapy

• Published in: Klinische Monatsblatter fur Augenheilkunde Vol. 225; no. 12; p. 1009
• Main Authors: Stieger, K, Lorenz, B
• Format: Journal Article
• Language: German
• Published: Germany 01.12.2008
• Subjects: Adenoviridae - genetics; Genetic Therapy - trends; Humans; Retinal Neovascularization - congenital; Retinal Neovascularization - genetics; Retinal Neovascularization - therapy; Retinitis Pigmentosa - congenital; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - therapy
• ISSN: 1439-3999
• DOI: 10.1055/s-2008-1027607

Over the last decade, significant progress has been made in the development of gene therapy strategies for the treatment of neovascular disorders and inherited dystrophies of the retina. Of all tested viral vectors, recombinant adeno-associated virus (rAAV) vectors, have been shown to be optimal vectors for gene transfer to the retina. Broadly speaking, two gene therapy strategies are used to treat retinal diseases; the first being corrective expression in the retina of the mutated gene (i. e., specific gene therapy) and the second being therapeutic expression of, for example, neurotrophic or antiangiogenic factors, in cases of neurodegenerative or neovascular, respectively, disorders (non-specific gene therapy). The naturally occurring RPE65 (-/-) Briard dog model has been successfully treated by specific gene transfer protocols and, based on these studies, the first clinical phase I trials are in preparation or have already begun. To avoid potential negative side effects due to the expression of neurotrophic and/or antiangiogenic factors in the retina, the expression of these transgenes needs to be regulated into a therapeutic window. Several regulatory systems have been tested in the retina of large animal models and may soon be used in clinical applications.