TARGETED IN VIVO GENE THERAPY FOR BRAIN TUMORS

描述：(申请人摘要)本申请的目的是 开发更好的载体和试剂，以改善基因 脑肿瘤的治疗。申请者的总体战略是新颖的和 规避至少在三个方面存在技术限制 从根本上说是重要的方式。首先，它允许定向递送 对癌细胞的特定基因，避免了大部分正常的 组织。其次，他的策略减少了许多重要的安全问题 与目前的基因治疗方法有关。最后，它改进了 关于基因传递的效率和可用的低病毒滴度。 申请人的战略包括具体交付修改后的 人嗜生态逆转录病毒受体(MERR)与靶细胞的结合。在.期间 MERR在这些细胞上表达的时间段 可被携带所需治疗药物的生态逆转录病毒感染 吉恩。他的技术的一个重要组成部分是使用单克隆 用于靶向人类肿瘤的抗体及其抗原结合域。 申请者将使用靶向成分，如抗体 与逆转录病毒受体结合，允许感染非 来自一个物种的允许细胞被来自另一个物种的病毒感染。为 例如，他将构建靶向之间的融合蛋白 成分(例如，单抗的VH和VL基因)和 受体。这种方法极大地增强了安全性，并提供了唯一 今天可用的基因治疗的靶向手段。申请人有 积累的大量初步数据表明，该方法 会奏效的。这个应用程序寻求完成体外研究，移动 将这项技术转化为动物模型，并最终转化为临床协议。

DESCRIPTION: (Applicant's Abstract) The purpose of this application is to develop better vectors and reagents that will improve the genetic therapy of brain tumors. The applicant's overall strategy is novel and circumvents present technological limitations in at least three fundamentally important ways. First, it permits the targeted delivery of specific genes to cancer cells, avoiding for the most part normal tissue. Second, his strategy reduces many important safety concerns associated with present gene therapy approaches. Finally, it improves on the efficiency of gene delivery and the low virus titers available. The applicant's strategy involves the specific delivery of the modified human ecotropic retrovirus receptor (MERR) to targeted cells. During the period in which MERR is expressed on those cells they will become infectable by ecotropic retroviruses carrying a desired therapeutic gene. An important component of his technology is the use of monoclonal antibodies and their antigen binding domains for targeting human tumors. The applicant will use targeting components, such as antibodies in conjunction with a retrovirus receptor to permit infection of non- permissive cells from one species by a virus from another species. For example, he will construct fusion proteins between the targeting component (e.g., VH and VL genes of a monoclonal antibody) and the receptor. This approach greatly enhances safety and provides the only means of targeting for gene therapy available today. The applicant has accumulated substantial preliminary data indicating that the approach will work. This application seeks to complete in vitro studies, move the technology into animal models and eventually to clinical protocols.