RETINA SPECIFIC GENE THERAPY WITH MODIFIED LIPOSOMES

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Currently there are no effective treatments that arrest the progression of retinitis pigmentosa and related disabling inherited retinal diseases. The discovery and cloning of the defective genes responsible for some of these diseases has given rise to the possibility of gene replacement, or somatic gene therapy. During the period of this award I intend to learn the fundamental cell and molecular biological techniques to become an independent physician-scientist investigator concentrating in somatic gene therapy techniques. To this end, The Emory University, Department of ophthalmology, has agreed to provide an ideal environment for me to achieve this goal through a combination of didactic, socratic, and practical experiences. As a result of my clinical training, I have a firm understanding of the pathophysiology, medical and surgical treatments of many retinal diseases. With John Nickerson, Ph.D., as my mentor, I will begin Phase I of the training period by attending graduate level classes directed at learning fundamental biological principles necessary to understand the retina on a cellular and molecular basis. In addition, during Phase I, I will begin laboratory work developing a novel gene delivery system that utilizes biologically active liposomes that have been shown in non-ocular tissue to dramatically increase transfection rates in vitro and in vivo as compared to other transfection systems. These liposomes will be modified further to target them specifically to the photoreceptor cell (Specific Aim #1). During Phase II of the training period, I will work more independently, remaining under the auspices Dr. Nickerson, to further develop this DNA vector system in a mouse animal model (Specific Aim #2). Finally, I will apply this gene vector system in an attempt to treat mice with inherited retinal degenerations (Specific Aim #3).