RETINA SPECIFIC GENE THERAPY WITH MODIFIED LIPOSOMES

目前还没有有效的治疗方法来阻止 视网膜色素变性和相关的致残性遗传性视网膜疾病。 发现和克隆缺陷基因， 这些疾病引起了基因替换的可能性，或者 体细胞基因疗法 在此期间，我打算学习 基本的细胞和分子生物学技术， 专注于体细胞基因研究的独立医生科学家 治疗技术 为此，埃默里大学，系 眼科，已经同意为我提供一个理想的环境， 实现这一目标，通过结合说教，苏格拉底， 实际经验。由于我的临床训练，我有一个公司 了解的病理生理学，医疗和手术治疗， 许多视网膜疾病。 约翰·尼克森博士作为我的导师我会 开始培训期的第一阶段，参加研究生水平的课程 旨在学习必要的基本生物学原理， 在细胞和分子的基础上了解视网膜。 此外，本发明还提供了一种方法， 在第一阶段，我将开始实验室工作，开发一种新的基因 利用生物活性脂质体的递送系统， 显示在非眼组织中显著增加转染率， 与其它转染系统相比，在体外和体内。 这些 脂质体将被进一步修饰以使它们特异性地靶向 感光细胞（具体目标#1）。 在第二阶段的培训中 期间，我将更加独立地工作，继续在博士的主持下工作。 为了在小鼠动物中进一步开发这种DNA载体系统， 具体目标#2）。 最后，我将把这个基因载体系统应用于 一种治疗遗传性视网膜变性小鼠的尝试（特异性 目标3）。

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).