HEPATOCYTE GROWTH-FACTOR EXPRESSED BY A RETROVIRUS-PRODUCING CELL-LINE ENHANCES RETROVIRAL TRANSDUCTION OF PRIMARY HEPATOCYTES - IMPLICATIONS FOR IN-VIVO GENE-TRANSFER

Hepatocyte Growth Factor (HGF) is the more potent mitogen of mature he patocytes. We have examined the effect of human HGF expression by a re combinant: retroviral cell line (MFG-LacZ) on retroviral transduction of primary mouse and human hepatocytes. The HGF in the supernatant of MFG-LacZ cell line was correctly processed and biologically active. Tr ansduction of mouse and human hepatocytes with the supernatant of tran sfected cells was increased 5-fold, as determined by beta-galactosidas e activity. The production of HGF was stable and did not interfere wit h the viral titers of the producer cells. This study provides evidence that expression of HGF within a retrovirus-producer cell line increas es the transduction rate of primary hepatocytes. Since the number of c orrected cells is a limiting step for phenotypic correction of liver d eficiencies, our approach should improve hepatic gene therapy efficien cy. Furthermore this cell line should be useful for in vivo liver gene therapy. (C) 1996 Academic Press, Inc.