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。这些病毒的致瘤作用是 转化蛋白是表达的，但我们已经证明，癌症 细胞可能会失去许多方面的恶性行为，当它们 暴露于人乳头瘤病毒的反义核酸。我们现在将优化使用 反义分子，最终目的是开发治疗 申请。我们将在E6和E7基因上筛选不同的位点 从而找到对HPV-18抑制最敏感的区域 反义寡核苷酸。我们将测量锤头的影响 寻找核酶是否比非核酶分子更有效。 我们将找到一种有效的方法将反义构建送到 口腔上皮细胞，通过比较几种病毒载体和启动子。这个 最有效的病毒载体将在裸鼠身上进行测试，以找到 该方法用于口腔癌基因治疗的可行性。这个 项目将在五年内开发到以下程度 治疗恶性及癌前病变的人体临床试验 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.