OCULAR GENE-THERAPY - EXPERIMENTAL STUDIES AND CLINICAL POSSIBILITIES

The Human Genome Project will identify, map and sequence all 50,000-10 0,000 human genes and will provide the tools to determine the genetic basis of both common and rare diseases, Understanding the genetic basi s of human disease will allow for the development of highly specific d rugs and for replacement of the altered gene through gene therapy, Gen e therapy may also be used to introduce a new function into cells with resulting therapeutic benefit. Genes map be delivered into cells in v itro or in vivo utilizing viral or nonviral vectors, Viral vectors whi ch have been used include retroviruses, adenoviruses, adeno-associated viruses and herpes viruses, Ocular disorders with the greatest potent ial for benefit of gene therapy at the current time include hereditary ocular diseases, including retinitis pigmentosa, tumors such as retin oblastoma or melanoma? and acquired proliferative and neovascular reti nal disorders, We have demonstrated the feasibility of ocular gene the rapy in a rabbit model of proliferative vitreoretinopathy, using retro viral vectors containing the herpes simples virus thymidine kinase 'su icide' gene, Although in vivo transduction efficiency is low, the stro ng bystander effect results in prominent killing of proliferating cell s in this model leading to inhibition of disease, In the future? gene therapy has the potential for the replacement of defective gene produc ts or introduction of new gene products into ocular cells, The selecti on of appropriate target genes and cells will be critical, as will the development of a methodology for safe, targeted gene transfer.