One of the major hurdles to successful gene therapy of genetic and acquired disease is the ability to introduce a foreign gene efficiently into the tissue of interest and, in the case of genetic diseases, achieve long-term transgene expression. Adenoviruses (Ads) have many attractive features which have made them a popular vehicle for gene transfer, including [1] well-defined biology, [2] the capacity to accommodate foreign DNA inserts up to 36 kb, and [3] the ability to infect a wide variety of cell types, tissues, and species in a cell cycle-independent fashion. Perhaps the most important quality of Ads is the fact that they are relatively safe, and are not associated with severe disease in immunocompetant individuals.