Regulation of the phosphoenolpyruvate carboxykinase/human factor IX gene introduced into the livers of adult rats by receptor-mediated gene transfer.

Gene transfer systems targeting the asialoglycoprotein receptor have been developed to introduce functional genes into cells in culture and livers of intact animals. A synthetic neoglycoprotein carrier was constructed and complexed to a chimeric gene containing the cDNA for human factor IX ligated to the promoter-regulatory region of the gene for phosphoenolpyruvate carboxykinase from the rat. The complex was used to transfect human hepatoma cells that express the asialoglycoprotein receptor. Human factor IX DNA sequences were found in cells 10 days after treatment. A 1.4 kB mRNA transcript was detected by Northern blot hybridization, which was inducible by treatment with dexamethasone or cAMP with theophylline. Western blot hybridization of proteins secreted into the culture medium detected human factor IX. The chimeric gene was also transferred into livers of rats using the neoglycoprotein carrier system after partial hepatectomy. Although the results were variable, the exogenous gene was transcribed in...