Assessment of the Efficacy of In Vivo CFTR Protein Replacement Therapy in CF Mice
| Autor: | Peter R. Durie, Christine E. Bear, Ling-Jun Huan, Keith A. Tanswell, Canhui Li, Mohabir Ramjeesingh, Geraldine Kent, Katalin Gyömörey, Michael Wilschanski, Cameron Ackerley, Yanchun Wang, Ernest Cutz |
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| Rok vydání: | 1998 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cell Membrane Permeability Cystic Fibrosis Neutrophils Proteolipids Cystic Fibrosis Transmembrane Conductance Regulator Cystic fibrosis Epithelium Membrane Potentials Amiloride Mice Drug Delivery Systems Protein replacement therapy Chlorides In vivo Genetics medicine Animals Molecular Biology Phospholipids Ion transporter Mice Knockout Drug Carriers Ion Transport Chemistry Cell Membrane respiratory system Apical membrane medicine.disease Transmembrane protein Cell biology Nasal Mucosa medicine.anatomical_structure Liposomes Chloride channel Molecular Medicine |
| Zdroj: | Human Gene Therapy. 9:521-528 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.1998.9.4-521 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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