Your browser version may not work well with NCBI's Web applications. More information here...
1: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15364-9. Epub 2003 Dec 12.
Related Articles, Links
Click here to read Click here to read Click here to read
Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia.

Koehler DR, Sajjan U, Chow YH, Martin B, Kent G, Tanswell AK, McKerlie C, Forstner JF, Hu J.

Programme in Lung Biology Research and Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.

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.

Publication Types:
PMID: 14673110 [PubMed - indexed for MEDLINE]

PMCID: PMC307573