The development of vectors for cell-specific delivery is of considerable interest for many cell biological studies. The present proposal describes a cell targeting strategy based on the use of the receptor for subgroup-A avian leukosis virus, TVA, to target retroviral vectors carrying genes of interest to a specific cell type in the mouse retina. The proposed studies are based on the idea that expression of the avian retroviral receptor, TVA, under a Muller cell-specific promoter renders Muller cells selectively susceptible to infection with the avian leukosis virus, and any gene carried by the infecting virus is expressed only in Muller cells. Therefore, the TVA-based retroviral system provides a novel opportunity to selectively and efficiently target the delivery and expression of any gene of interest in the Muller cell. Specifically, the proposed experiments will investigate whether GFAP promoter can be used to selectively expressing TVA in Muller cells. Subsequent studies wiill examine whether intraocular injection of the retrovirus, HIV GFP(ALSV-A), in GFAP-tv-a transgenic mice, results in Green Fluorescent Protein (GFP) expression specifically in Muller cells. Although the focus of the present proposal is to target genes to Muller cells, the TVA-based system has a much broader scope in retinal cell and molecular biological research. With a judicious choice of cell typespecific promoter, it should be possible to selectively and efficiently target the delivery and expression of any gene of interest to a specific retinal cell type. In summary, the TVA-system offers a novel, exciting approach for delivering genes of interest to specific retinal cells, and can be expected to have a major impact on future studies in retinal cell biology. ? ? ?
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