INHIBITION OF PAPILLOMAVIRUSES IN ORAL EPITHELIUM

某些类型的人乳头瘤病毒（HPV）存在于肿瘤中 许多口腔癌的细胞。 这些病毒是致瘤性的， 转化蛋白的表达，但我们已经表明， 当细胞被破坏时，它们可能会失去许多恶性行为的方面。 暴露于HPV的反义核酸。 我们现在将优化使用 反义分子，最终目的是开发治疗 应用. 我们将筛选E6和E7基因上的不同位点， HPV-18，以便找到最敏感的抑制区域， 反义寡核苷酸 我们将测量锤头鲨的影响 核酶来发现它们是否比非核酶分子更有效。 我们将找到一种有效的方法， 口腔上皮细胞，通过比较几种病毒载体和启动子。 的 最有效的病毒载体将在裸鼠中进行测试， 该方法用于人口腔癌基因治疗的可行性。 的 该项目将在五年内开发， 恶性和癌前病变治疗的人体临床试验 将是可能的。

Certain types of the human papillomavirus (HPV) are present in the tumor cells of many oral cancers. These viruses are tumorigenic when their transforming proteins are expressed, but we have shown that the cancer cells may lose many aspects of their malignant behavior when they are exposed to antisense nucleic acids of HPV. We will now optimize the use of antisense molecules, with the ultimate aim of developing therapeutic applications. We will screen different sites on the E6 and E7 genes of HPV-18 so as to find the most sensitive regions for inhibition by antisense oligonucleotides. We will measure the effects of hammerhead ribozymes to find if they are more effective than non-ribozyme molecules. We will find an effective method of delivering antisense constructs to oral epithelium, by comparing several virus vectors and promoters. The most effective virus vectors will then be tested in nude mice to find the feasibility of this method of gene therapy for human oral cancer. The project will be developed over a five-year period to the point where human clinical trials of therapy for malignant and premalignant lesions will be possible.