ADVANCED GENERATION VECTORS FOR CANCER GENE THERAPY

描述：(申请人的描述)本提案的目的是 通过开发有能力的载体促进肿瘤疾病的基因治疗 高效和细胞特异性的基因传递。我们的假设是 可以对腺病毒载体进行基因修改，以改变其固有的 靶肿瘤实现选择性转导的病毒亲和性 细胞。为此，我们的特定目标是定义展示 腺病毒载体与靶肿瘤细胞的特异性结合 重定向方法；开发展示肿瘤结合肽的方法 腺病毒六邻体衣壳蛋白中的载体重定向 方法：通过腺病毒载体展示肿瘤特异性基因的传递 被修饰为在修饰的六邻体蛋白中含有肿瘤结合肽；以及 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，这方面的发展 载体系统将代表着基因治疗的重大技术进步 肿瘤疾病。 建议的商业应用：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