STABLE AND EFFICIENT GENE-TRANSFER INTO THE RETINA USING AN HIV-BASEDLENTIVIRAL VECTOR

The development of methods for efficient gene transfer to terminally d ifferentiated retinal cells is important to study the function of the retina as well as for gene therapy of retinal diseases. We have develo ped a lentiviral vector system based on the HIV that can transduce ter minally differentiated neurons of the brain in vivo. In this study, we have evaluated the ability of HIV vectors to transfer genes into reti nal cells. An HIV vector containing a gene encoding the green fluoresc ent protein (GFP) was injected into the subretinal space of rat eyes. The GFP gene under the control of the cytomegalovirus promoter was eff iciently expressed in both photoreceptor cells and retinal pigment epi thelium. However, the use of the rhodopsin promoter resulted in expres sion predominantly in photoreceptor cells. Most successfully transduce d eyes showed that photoreceptor cells in > 80% of the area of whole r etina expressed the GFP. The GFP expression persisted for at least 12 weeks with no apparent decrease. The efficient gene transfer into phot oreceptor cells by HIV vectors will be useful for gene therapy of reti nal diseases such as retinitis pigmentosa.