title: Assessment of the efficacy of in vivo CFTR protein replacement therapy in CF mice.
abstract: Cystic Fibrosis (CF) is caused by mutations in the CF gene that lead, for the most part, to mislocalization of the protein product, the cystic fibrosis transmembrane conductance regulatory (CFTR). CFTR is a chloride channel normally situated in the apical membrane of epithelial cells where it contributes to transepithelial ion transport. In this study we demonstrated the feasibility of in vivo transfer of purified CFTR protein via phospholipid liposomes into the apical membrane of nasal epithelia of CFTR knockout mice. Membrane incorporation of immunogold-labeled CFTR could be visualized by electron microscopy and correction of CF-related defects in ion transport measured by nasal potential difference (PD) measurements in about one-third of the animals treated. Although these initial results are promising, effectiveness of this therapeutic approach appears to be limited by the inefficient incorporation of CFTR into the apical epithelial cell membrane.
authors.affiliation: Division of Cell Biology, Research Institute at the Hospital for Sick Children, Toronto, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Ramjeesingh
authors.forename: L J
authors.initials: LJ
authors.lastname: Huan
authors.forename: M
authors.initials: M
authors.lastname: Wilschanski
authors.forename: P
authors.initials: P
authors.lastname: Durie
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Gyomorey
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Kent
authors.forename: K A
authors.initials: KA
authors.lastname: Tanswell
authors.forename: E
authors.initials: E
authors.lastname: Cutz
authors.forename: C
authors.initials: C
authors.lastname: Ackerley
authors.forename: C E
authors.initials: CE
authors.lastname: Bear
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000008:administration & dosage* / Q000032:analysis / Q000276:immunology / Q000502:physiology; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004848:Epithelium / Q000737:chemistry / Q000276:immunology; D017136:Ion Transport; D008081:Liposomes; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000737:chemistry / Q000502:physiology; D009504:Neutrophils; D010743:Phospholipids; D011510:Proteolipids
chemical_list: D002712:Chlorides; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; D011510:Proteolipids; C020485:proteoliposomes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride