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 deliver and express therapeutic genes preferentially into specific cell populations. This can be achieved by the manipulation of viral proteins mediating target-cell recognition, as well as by the introduction of tissue-specific promoters into viral vectors. As a first approach towards this goal, we describe here the construction and testing of a recombinant adenovirus expressing the lacZ gene encoding beta-galactosidase under the control of 2 kilobase pairs (kbp) of 5' untranslated DNA sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We show that such a recombinant virus directs beta-galactosidase 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 paralleling that of the endogenous CFTR gene. This data indicates that only part of the natural CFTR gene regulation is reconstituted in such a vector.