Ke. Drazan et al., HEPATIC-FUNCTION IS PRESERVED FOLLOWING LIVER-DIRECTED, ADENOVIRUS-MEDIATED GENE-TRANSFER, The Journal of surgical research, 59(2), 1995, pp. 299-304
Inherited and acquired disorders of the liver are attractive targets f
or gene therapy. Hepatic cells are susceptible targets for shuttle vec
tors because of a diversity of protein and viral receptors and accessi
bility of a selective afferent blood supply. Preservation of existing
hepatic cell integrity and metabolic function is of paramount importan
ce for successful whole animal gene therapy trials. In this report, we
examine hepatic cell function and integrity following adenovirus-medi
ated reporter gene transfer to the liver in vivo. El-deleted, replicat
ion-defective adenovectors encoding the LacZ gene driven by the human
CMV promoter were delivered to the liver by isolated portal perfusion.
The gene transfer rate, as determined by specific histochemical stain
ing, approached 30% with recombinant protein detectable by Western blo
t throughout the course of study. Hepatic cell integrity as assessed b
y histology and hepatic enzyme profile (serum aspartate aminotransfera
se, gamma-glutamyl transpeptidase) demonstrated normal cellular archit
ecture and no significant difference between transfected liver and con
trols. Hepatic synthetic and metabolic function, as determined by albu
min levels, prothrombin time, and bilirubin, were similar between the
two study groups. This study demonstrates that efficient adenovirus-me
diated gene transfer and expression in the rat liver do not compromise
hepatic cell metabolism and integrity. (C) 1995 Academic Press, Inc.