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        Gene Transfer into Cystic Fibrosis Airway Epithelial Cells

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        513
        Gene transfer into airway epithelial cells becomes a particularly motivating goal as far as cystic fibrosis (CF) is concerned. As mentioned in Chapter 15 , approx 90% of deaths caused by this devastating disease are the result of infections of the respiratory tract owing to dysfunction of the Cl- transport in airway epithelial cells. Efficient transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene into the airway epithelium of CF patients in vivo is one of the current challenges of gene therapists, and much is being made in that direction in the United States, Europe, and Argentina. The airway epithelium has a very slow turnover, with presumably only l–2% of cells at division at a given time. Therefore, retroviruses are not the most suitable vector system for gene transfer of the CF gene (1 ). Adenovirus vectors, adeno-associated virus vectors, or liposomes are being tested in the gene therapy clinical trials currently going on (2 , 3 ). In vitro CF gene transfer into airway epithelial cells has relevance in the optimization of gene transfer vectors, of CFTR activity tests, of endogenous as well as vector-produced CFTR-mRNA analysis, and so forth, related to the in vivo application. In the following sections, analysis will restrict itself to in vitro gene transfer approaches.
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