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，质膜氯化物通道。 死亡的主要原因 CF患者由于无法清除而导致的并发症 肺部的粘液正确。 如果缺失或 CF患者的肺呼吸道内壁的细胞中有缺陷 替换，正常功能可以恢复。 由蛋白质脂质体组成 跨越磷脂囊泡双层的CFTR蛋白 将构建适当的方向。 吸入这些气溶胶 蛋白质脂质体随后融合脂质体与顶端融合 气道上皮细胞的膜应导致CFTR为 送到适当的位置，希望能够恢复一些普通的粘液 分泌。 最初，将通过给出这些方法来检查这些方法 CFTR脂质体对组织培养的人类细胞并确定是否是否 CFTR可以引入细胞膜。 模型膜蛋白 从兔子血液中分离出来将注入大鼠的肺中， 兔子证明在递送膜蛋白的可行性 脂质体。 一旦解决了适当的条件，CFTR 蛋白质也将递送到动物肺部。