TARGETING CELL-SPECIFIC GENE-EXPRESSION WITH AN ADENOVIRUS VECTOR CONTAINING THE LACZ GENE UNDER THE CONTROL OF THE CFTR PROMOTER

In vivo gene therapy requires the development of vectors able to deliv er and express therapeutic genes preferentially into specific cell pop ulations. This can be achieved by the manipulation of viral proteins m ediating target-cell recognition, as well as by the introduction of ti ssue-specific promoters into viral vectors. As a first approach toward s this goal, we describe here the construction and testing of a recomb inant adenovirus expressing the lacZ gene encoding beta-galactosidase under the control of 2 kilobase pairs (kbp) of 5' untranslated DNA seq uences of the cystic fibrosis transmembrane conductance regulator (CFT R) gene. We show that such a recombinant virus directs beta-galactosid ase expression in cell lines expressing CFTR, and in human and murine respiratory tract cells in vitro and in vivo. However, we were unable to demonstrate a cell-type specificity of expression strictly parallel ing that of the endogenous CFTR gene. This data indicates that only pa rt of the natural CFTR gene regulation is reconstituted in such a vect or.