ADVANCED GENERATION VECTORS FOR CANCER GENE THERAPY

描述：（申请人的描述）本提案的目标是 通过开发一种载体来促进肿瘤疾病的基因治疗， 高效和细胞特异性的基因传递。 我们假设 可以对腺病毒载体进行遗传修饰以改变其天然的 病毒嗜性以实现靶肿瘤的选择性转导 细胞 为此，我们的具体目标是定义肽，其表现出 用于腺病毒载体中与靶肿瘤细胞的特异性结合 重靶向方法;开发展示肿瘤结合肽的方法 在载体重靶向背景下的腺病毒六邻体衣壳蛋白中 方法;证明通过腺病毒载体的肿瘤特异性基因递送 修饰以在修饰的六邻体蛋白内含有肿瘤结合肽;和 为了制备和验证使用这些重定向的新型腺病毒载体， 癌症背景下人类临床基因治疗试验的原则 卵巢 通过解决限制翻译的关键问题， 将基因治疗策略引入临床试验， 载体系统将代表基因治疗的主要技术进步， 肿瘤性疾病 拟议商业应用：不可用

DESCRIPTION: (Applicant's Description) It is the goal of this proposal to facilitate gene therapy for neoplastic diseases by developing a vector capable of efficient and cell-specific gene delivery. It is our hypothesis that genetic modifications can be made to the adenoviral vector to alter its native viral tropism in order to achieve selective transduction by target tumor cells. To this end, our specific aims are to define peptides which exhibit specific binding to target tumor cells for employment in adenoviral vector retargeting approaches; to develop methods to display tumor binding peptides in hexon capsid protein of adenovirus in the context of vector retargeting approaches; to demonstrate tumor specific gene delivery via adenoviral vectors modified to contain tumor binding peptides within modified hexon proteins; and to prepare and validate novel adenoviral vectors employing these retargeting principles for human clinical gene therapy trials in the context of cancer of the ovary. By addressing the key issue which limits the translation of present gene therapy strategies into clinical trials, the development of this vector system would represent a major technical advance in gene therapy for neoplastic diseases. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE