ADENOVIRAL VECTORS GIVEN INTRAVENOUSLY TO IMMUNOCOMPROMISED MICE YIELD STABLE TRANSDUCTION OF THE COLONIC EPITHELIUM

Background & 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 i njected intravenously with a recombinant adenovirus, higher levels of a reporter gene are expressed in the colon than in the liver. Methods: Adenovirus encoding beta-galactosidase was injected intravenously in lethally irradiated B6D2F1 mice that had received syngeneic B6D2F1 bon e 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 colonic tissue ob tained months after transduction. Colonic tissues were also stained fo r beta-galactosidase. Results: Intravenous adenoviral administration y ielded long-term expression of a foreign gene in liver and colonic epi thelium in transiently immunocompromised recipients. Histological anal ysis suggested that stem cell transfection and integration of the fore ign gene may have occurred insofar as crypts and colonic epithelial ce lls in immunocompromised animals stained positive for beta-galactosida se months after virus administration. In polymerase chain reaction ana lysis, the transverse and distal colon of syngeneic bone marrow transp lant recipients showed long-term retention of beta-galactosidase gene. Conclusions: Long-term transduction of colonic epithelial cells is ob served after administration of adenoviral vectors by an intravenous ro ute in selectively immunocompromised mice.