Adeno-associated viral gene therapy for retinal disorders

Abstract

Gene therapy is ideally suited to the treatment of inherited retinal degenerations in order to prevent blindness. The target area of the outer retina is small and relatively immune privileged, which facilitates the delivery of small volumes of vector without generating signifi cant immune reactions. Moreover, most of the currently untreatable forms of blindness have a genetic component, either monogenic such as in retinitis pigmentosa or as a result of several genes interacting along a common pathway, such as age-related macular degeneration, the commonest cause of legal blindness in the developed world. The self-contained nature of the eye also facilitates the application of gene therapy for sustained expression of intraocular proteins, such as inhibitors of angiogenesis or growth factors that might confer neuroprotection to dying cells. In this chapter, we review the indications and applications of gene therapy, concentrating specifi cally on adeno-associated viral (AAV) vectors, describing the protocols for production and administration of AAV vectors to the eye in the laboratory setting.