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.
NIH ExPorter
NIH ExPorter