Delivery of genes to the eye using lentiviral vectors.

Abstract

The primary aim of gene transfer into the retinal cells has been to investigate the developmental mechanisms of the retinal cells or to reverse retinal diseases. Retroviruses have been used to investigate the differentiation of retinal cells, to study the embryonic retina in vivo or explant organ culture, and to trace the fate of the cells that were dividing at the time of gene transfer. Using adenovirus, Bennett et al. showed the possibility of using gene therapy to correct degenerative diseases of the central nervous system (CNS) (6). However, owing to the short duration of the gene expression, adenovirus is not suitable for correcting chronic diseases. Currently, lentivirus (7-9) and adenoassociated virus vectors (10-14) are being used for studying and correcting gene therapy of retinal degenerative diseases. Using an HIV vector carrying the green fluorescent protein (GFP) gene expressed from the cytomegalovirus (CMV) promoter, we showed that efficient and long-lasting gene expression could be obtained in the retina (7,8). Moreover, gene expression was restricted to the photoreceptor cells and was more efficient with the rhodopsin promoter. Similar results were reported using adeno-associated virus (AAV) vector. Using a lentivirus vector carrying the phosphodiesterase beta subunit (PDEbeta) gene, the mutation of which causes retinal degeneration called retinitis pigmentosa in rd mice, photoreceptor cells were rescued from degeneration in rd mice for at least 6 mo by PDEbeta transduction using HIV-based lentivirus vector (9).