CONTROL OF TRANSGENE EXPRESSION IN CUTANEOUS ENDOTHELIUM

本申请描述了更好的靶向的替代方案， 通过非特异性地递送非活性遗传物质来实现 然后用光局部激活。 该提案基于小说 临时改变质粒DNA以阻断转录策略。 一个 这种失活策略重要特征是恢复 跨细胞递送后的转录可以通过局部化的 光到目标皮肤区域。 靶向递送治疗剂 将遗传物质转移到皮肤的内皮是困难的，特别是 用于非病毒递送方法。 总的来说，目标问题 被认为取决于两个关键步骤：（1）提供 基因向靶细胞群体的转移和（2）其随后的表达。 假设提高有针对性的交付的效率将 克服明显的低表达率，一些实验室 我试图通过关注第一步来改进非语言方法， 并因此寻求提高目标的运载工具的特异性 细胞 我们建议测试这种新的靶向策略， 特别适用于某些皮肤病， 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.