Adenoviral vectors given intravenously to immunocompromised mice yield stable transduction of the colonic epithelium

Background and Aims: Adenoviral vectors have been used for gene transfer in the liver but not for gene transfer in intestinal tissue. The aim of this study was to show that in selectively immunocompromised mice injected intravenously with a recombinant adenovirus, higher levels of a reporter gene are expressed in the colon than in the liver. Methods: Adenovirus encoding β-galactosidase was injected intravenously in lethally irradiated B6D2F1 mice that had received syngeneic B6D2F1 bone marrow and spleen cell transplants, in athymic mice, in mice treated with 2-chlorodeoxyadenosine, or in normal mice. Enzymatic assays and polymerase chain reaction analysis were performed on coIonic tissue obtained months after transduction. Colonic tissues were also stained for β-galactosidase. Results: Intravenous adenoviral administration yielded long-term expression of a foreign gene in liver end coIonic epithelium in transiently immunocompromised recipients. Histological analysis suggested that stem cell transfection and integration of the foreign gene may have occurred insofar as crypts and colonic epithelial cells in immunocompromised animals stained positive for β- galactosidase months after virus administration. In polymerase chain reaction analysis, the transverse and distal colon of syngeneic bone marrow transplant recipients showed long-term retention of β-galactosidase gene. Conclusions: Long-term transduction of coIonic epithelial cells is observed after administration of adenoviral vectors by an intravenous mute in selectively immunocompromised mice.