ABSTRACT

Bioactive compounds can be selectively delivered to or activated in specific tissues on the basis of their physical, chemical, and metabolic properties. Such considerations have provided the fundamental principles underlying modern medical pharmacology. The lung is a complex organ containing more than 40 cell types, each with distinct morphological and biochemical properties. The respiratory epithelium consists of distinct populations of columnar cells lining the conducting and peripheral airways. The unique accessibility of these cells, by instillation or inhalation, makes the lung an ideal target for gene therapy. Recombinant viral vectors, including adenoviruses, retroviruses, and adeno-associated viruses, enter target cells based on presence of viral proteins that interact with cell surfaces. Respiratory epithelial cells of the conducting and peripheral airways display a variety of morphological and biochemical features. Site specific mutagenesis of elements in this region completely block transcriptional activity of promoter constructs containing this region.