CONTROL OF TRANSGENE EXPRESSION IN CUTANEOUS ENDOTHELIUM

这个应用程序描述了一种更好定位的替代方案，即 通过非特异性地传递非活性遗传物质实现的 然后用光进行局部激活。这项建议是基于小说 暂时改变质粒DNA以阻止转录的策略。一个 这一停用策略重要特征是恢复 跨细胞传递后的转录可以通过局部化实现 光线照射到目标皮肤区域。靶向输送治疗性药物 遗传物质对皮肤内皮细胞是困难的，尤其是 用于非病毒递送方法。总体而言，目标问题 被视为依赖于两个关键步骤：(1)交付 基因与靶细胞群体的结合以及(2)其随后的表达。 假设提高定向递送的效率将 克服了明显的低表达率，一些实验室 我试图通过专注于第一步来改进非语言方法 并因此寻求提高递送工具对目标的专一性 细胞。我们建议测试这一新的目标策略，它可能是 对某些内皮细胞改变的皮肤病特别有用 这种功能可能会阻止或逆转疾病的进展。

This application describes an alternative to better targeting which is achieved by delivery of inactive genetic material non-specifically followed by local activation with light. This proposal is based on novel strategy to temporarily alter plasmid DNA to block transcription. An important feature of this inactivation strategy is that restoration of transcription after transcellular delivery can be achieved by localized light to the targeted skin region. Targeted delivery of therapeutic genetic material to the endothelium of the skin is difficult, particularly for non-viral delivery methodologies. In general, the targeting problem has been viewed as dependent on two critical steps: (1) delivery of the gene to the target cell population and (2) its subsequent expression. Hypothesizing that increasing the efficiency of targeted delivery will overcome apparently low expression rates, a number of laboratories have sought to improve nonverbal methods by focusing on the first step and hence seek to enhance the specificity of delivery vehicles for target cells. We propose to test this novel targeting strategy which may be particularly useful in some skin diseases in which altered endothelial function might block or reverse the progression of disease.