TARGETED IN VIVO GENE THERAPY FOR BRAIN TUMORS

针对脑肿瘤的体内基因治疗

• 批准号: 2458202
• 负责人: DANIEL MERUELO
• 金额: $ 24.55万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458202
• 关键词: TARGETED; VIVO; GENE; THERAPY; BRAIN

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.

描述：（申请人的摘要）此申请的目的是 开发更好的向量和试剂，以改善遗传 脑肿瘤的治疗。申请人的整体策略是新颖的， 规避至少三个 从根本上重要的方法。首先，它允许目标交付 癌细胞的特定基因，大部分避免正常 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相关。最后，它有所改善 关于基因输送的效率和低病毒滴度的可用效率。 申请人的策略涉及修改后的特定交付 人类生态逆转录病毒受体（MERR）对靶细胞。期间 在这些单元上表达MERR的时期，它们将成为 可通过携带所需治疗的生态逆转录病毒感染 基因。他技术的重要组成部分是使用单克隆 抗体及其抗原结合结构域用于靶向人类肿瘤。 申请人将使用靶向组件，例如 与逆转录病毒受体的结合以允许感染非 - 来自另一种物种的病毒来自一种物种的允许细胞。为了 例如，他将在靶向之间构建融合蛋白 成分（例如，单克隆抗体的VH和VL基因）和 受体。这种方法大大提高了安全性，并提供了唯一的 靶向基因疗法的方法。申请人有 积累了大量的初步数据，表明该方法 会起作用。该应用程序旨在完成体外研究，移动 该技术进入动物模型，并最终进入临床方案。