Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia
| Autor: | Jim Hu, Yu Hua Chow, Geraldine Kent, Umadevi S. Sajjan, Bernard Martin, David R. Koehler, A. Keith Tanswell, Colin McKerlie, Janet F. Forstner |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Genetic enhancement Genetic Vectors Cystic Fibrosis Transmembrane Conductance Regulator Inflammation Respiratory Mucosa Biology Transfection Cystic fibrosis Viral vector Mice Chlorocebus aethiops medicine Animals Humans Lung Respiratory Tract Infections Mice Knockout Analysis of Variance Multidisciplinary Burkholderia Infections Genetic Therapy Biological Sciences respiratory system medicine.disease Cystic fibrosis transmembrane conductance regulator respiratory tract diseases medicine.anatomical_structure Gene Expression Regulation COS Cells Immunology Knockout mouse biology.protein medicine.symptom |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:15364-15369 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2436478100 |
| Popis: | We developed a helper-dependent adenoviral vector for cystic fibrosis lung gene therapy. The vector expresses cystic fibrosis transmembrane conductance regulator ( Cftr ) using control elements from cytokeratin 18 . The vector expressed properly localized CFTR in cultured cells and in the airway epithelia of mice. Cftr RNA and protein were present in whole lung and bronchioles, respectively, for 28 days after a vector dose. Acute inflammation was minimal to moderate. To test the therapeutic potential of the vector, we challenged mice with a clinical strain of Burkholderia cepacia complex (Bcc). Cftr knockout mice (but not Cftr +/+ littermates) challenged with Bcc developed severe lung histopathology and had high lung bacteria counts. Cftr knockout mice receiving gene therapy 7 days before Bcc challenge had less severe histopathology, and the number of lung bacteria was reduced to the level seen in Cftr +/+ littermates. These data suggest that gene therapy could benefit cystic fibrosis patients by reducing susceptibility to opportunistic pathogens. |
| Databáze: | OpenAIRE |
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