STRAIN RELATED VARIATIONS IN ADENOVIRALLY MEDIATED TRANSGENE EXPRESSION FROM MOUSE HEPATOCYTES IN-VIVO - COMPARISONS BETWEEN IMMUNOCOMPETENT AND IMMUNODEFICIENT INBRED STRAINS

High efficiency gene transfer and gene expression in hepatocytes in vi vo can be achieved using recombinant adenoviral vectors. However, the persistence of gene expression in different experimental animal models has been variable. To determine if similar differences could be obser ved in a single species, persistence of gene expression was studied in inbred strains of mice using a recombinant adenoviral vector that exp resses human alpha 1-antitrypsin. Marked variability in the persistenc e of gene expression ranging from several weeks (C3H/HeJ and Balb/c) t o more than 3 months [C57Bl/6, B10.A(2R) and B10.BR] was observed when this vector was transduced in different strains of inbred mice. This variability did not correlate with H-2 type. To evaluate the role of T and B cell immunity in the persistence of gene expression, congenic C 3H-scid and Balb/c-scid mice were studied and found to have indefinite gene expression from transduced hepatocytes. These animals unlike the ir immunocompetent counter-parts were able to undergo secondary transd uction of hepatocytes with a different recombinant adenoviral vector. These findings suggest that as yet unidentified genetic loci influence the persistence of adenovirus-mediated hepatic gene expression in viv o, and these effects are mediated at least in part, by the antigen spe cific immune system.