DELIVERY OF CFTR TO AIRWAY EPITHELIA IN PROTEOLIPOSOMES

通过蛋白脂质体将 CFTR 递送至气道上皮

• 批准号: 3369213
• 负责人: MARTIN TEINTZE
• 金额: $ 17.02万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3369213
• 关键词: Baculoviridae; band 3 protein; chloride channels; cystic fibrosis; laboratory rabbit; laboratory rat; liposomes; membrane fusion; protein purification; recombinant DNA; respiratory epithelium; tissue /cell culture

Cystic fibrosis (CF) is caused by mutations in the gene for the CFTR protein, a plasma membrane chloride channel. The primary cause of death in CF patients is due complications resulting from their inability to clear mucus from the lungs properly. If the CFTR protein that is missing or defective in the cells lining the airway of the lungs in CF patients can be replaced, normal function may be restored. Proteoliposomes consisting of the CFTR protein spanning the bilayer of phospholipid vesicles in the proper orientation will be constructed. Inhalation of an aerosol of these proteoliposomes followed by fusion of the liposomes with the apical membrane of the airway epithelial cells should result in CFTR being delivered to its proper location, hopefully restoring some normal mucous secretion. Initially this methodology will be examined by giving these CFTR liposomes to human cells in tissue culture and determining whether the CFTR can be introduced into the cell membrane. A model membrane protein isolated from rabbit blood will be infused into the lungs of rats and rabbits to demonstrate the feasibility of delivering membrane proteins in liposomes. Once the proper conditions have been worked out the CFTR protein will also be delivered to animal lungs.

囊性纤维化 (CF) 是由 CFTR 基因突变引起的 蛋白质，质膜氯离子通道。 死亡的主要原因 CF患者是由于无法清除而引起的并发症 适当排出肺部粘液。 如果 CFTR 蛋白缺失或 CF 患者肺部气道内壁细胞有缺陷 更换后即可恢复正常功能。 蛋白脂质体由以下组成 CFTR 蛋白跨越磷脂囊泡双层 将构建正确的方向。 吸入这些气溶胶 蛋白脂质体，然后脂质体与顶端融合 气道上皮细胞膜的破坏应导致 CFTR 运送到正确的位置，希望恢复一些正常的粘液 分泌。 最初，将通过给出这些来检查该方法 CFTR脂质体对组织培养中的人体细胞的影响并确定是否 CFTR可以被引入到细胞膜中。 模型膜蛋白 从兔血中分离出来的物质将被注入大鼠的肺部 兔子证明了在体内传递膜蛋白的可行性 脂质体。 一旦确定了适当的条件，CFTR 蛋白质也将被输送到动物肺部。