Novel BIV-based vectors with retina-specific promoter

描述（由申请人提供）：湿性年龄相关性黄斑变性（AMD）和糖尿病增殖性视网膜病变（DPR）中发生的脉络膜新生血管化（CNV）是一种导致严重视力丧失和失明的慢性过程。CNV的特征是异常新血管从脉络膜毛细血管通过布鲁赫膜缺陷生长到视网膜下间隙。目前正在开发的产品由于需要重复和不方便的眼内注射而受到严重影响。因此，需要更好的输送系统。用抗血管生成因子治疗CNV的策略是非常有前途的。CytoPro的目标策略是，基因转移载体的单次眼内给药将提供选择性地向视网膜持续递送治疗性抗血管生成蛋白。CytoPro目前正在开发一种先进的基因转移系统，用于有效的抗血管生成转基因，以快速开发一种上级产品，并将其用于CNV治疗。 在接下来的几个月里，该SBIR项目的I期研究的目标是开发一种来自人Pax 6 PO启动子的Cyto-PO启动子，用于使用慢病毒转移系统进行基因递送和表达。在该项目的第一阶段，我们计划：1）优化Cyto-PO启动子的效率和视网膜特异性; 2）替换慢病毒转移载体中的病毒来源CMV启动子; 3）评估新的lenti-Cyto-PO载体介导的基因表达在视网膜服务细胞中的特异性、效率和稳定性。我们相信，I期研究的目标将是为II期研究积累足够的数据，即lenti-Cyto-PO载体系统将在小鼠视网膜中用作载体，以转移编码抗血管生成肽和siRNA的转基因，以保护缺氧诱导的CNV。这种组织特异性慢病毒转移系统具有巨大的商业价值，因为它将非常有效地用于治疗退行性眼病中的CNV。

DESCRIPTION (provided by applicant): Choroidal NeoVascularization (CNV) occurring in wet age-related macular degeneration (AMD) and diabetic proliferative retinopathy (DPR) is a chronic process leading to severe visual loss and blindness. CNV is characterized by growth of abnormal, new blood vessels from the choriocapillaris through defects in the Bruch's membrane into the sub-retinal space. The products currently in development are significantly compromised by the requirement for repeated and inconvenient intraocular injection. Thus, a better delivery system is needed. The strategy of treating CNV with anti-angiogenic factors is very promising. CytoPro aims the strategy that a single intra-ocular administration of a gene transfer vector will provide sustained delivery of a therapeutic, antiangiogenic protein selectively to the retina. CytoPro is now developing an advanced gene transfer system for potent anti-angiogenic transgenes to rapidly develop a superior product and to market it for CNV treatments. The goal of Phase I study of this SBIR project in the next few months is to develop a Cyto-PO promoter derived from human Pax6 PO promoter for gene delivery and expression using a lentiviral transfer system. In phase I of the project, we plan to: 1) optimize the efficiency and retina-specificity of the Cyto-PO promoter; 2) replace the viral origin CMV promoter in the lentiviral transfer vector; and 3) evaluate the specificity, efficiency and stability of the new lenti-Cyto-PO vector-mediated gene expression in retina-serived cells. We believe that objectives of phase I studies will be to accrue sufficient data for phase II studies that lenti-Cyto-PO vector system will be used in the retina of mice as a vehicle to transfer transgenes encoding anti-angiogenic peptides and siRNA to protect hypoxia-induced CNV. This tissue-specific lentiviral transfer system has tremendous commercial values because it will be very effective for the use of treating CNV in degenerative ocular diseases.