TARGETING GENES TO CELLS RELEVANT TO CYSTIC FIBROSIS

将基因靶向与囊性纤维化相关的细胞

• 批准号: 2143450
• 负责人: Pamela B Davis
• 金额: $ 19.32万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2143450
• 关键词: antibody receptor; antireceptor antibody; basolateral membrane; clone cells; cystic fibrosis; gene expression; gene therapy; genetic disorder; genetic manipulation; glycoproteins; immunocytochemistry; liver; lung; monoclonal antibody; postmortem; respiratory epithelium; tissue /cell preparation; transfection

DESCRIPTION (adapted from the application): The long term objective of this project is to develop methods for gene therapy of cystic fibrosis (CF). The project has two specific aims. The first aim is to identify the cells that express the cystic fibrosis transmembrane conductance regulator (CFTR) in the lung. This will be done by using monoclonal antibodies to CFTR. The second specific aim is to develop the molecular tools that are needed to deliver and stably express genes in those cells. The tissue specific expression of the polymeric immunoglobulin receptor (pIgR) will be used to target non-degradative internalization of macromolecules from the basolateral surface. A Fab fragment of antibody to pIgR covalently coupled to a polycation link to DNA will be used to direct foreign DNA into the desired cells. The specificity of the targeting will be determined and uptake and expression of the DNA optimized.

说明(改编自申请)：的长期目标 本项目旨在开发囊性纤维化的基因治疗方法。 (Cf)。该项目有两个具体目标。第一个目标是确定 表达囊性纤维化跨膜电导调节因子的细胞 (Cftr)在肺部。这将通过使用单克隆抗体来完成 CFTR。第二个具体目标是开发分子工具，这些工具是 需要在这些细胞中传递和稳定表达基因。组织 聚合免疫球蛋白受体(PIgR)的特异性表达将是 用于靶向大分子的非降解内化 基准面。抗pIgR共价偶联抗体的Fab片段 连接到DNA的聚阳离子连接将被用来将外来DNA引导到 所需单元格。目标的特殊性将被确定，并 DNA的摄取和表达进行了优化。