Hepatic control elements promote long‐term expression of human coagulation factor IX gene in hydrodynamically transfected mice

AbstractBackgroundLong‐term expression of the delivered target gene is critical for successful gene therapy. Recently, hepatic control region I (HCR I) originating from the apolipoprotein (apo)C‐I pseudogene was shown to be a critical element for long‐term gene expression in the liver of mice. HCR II is another hepatic control region of apoC‐I.MethodsHCR I, HCR II and HCR I/II‐containing plasmids encoding factor IX were prepared and hydrodynamically transferred into the liver of normal and hemophilia B mice. Factor IX expression, clotting activity and formation of antibodies against the expressed gene product were compared.ResultsHCR I‐, HCR II‐ and HCR I/II‐containing plasmids all induced long‐term gene expression in both normal and hemophilia B mice. Post‐transfection factor IX expression in the hemophilia B mice remained above 500 ng/ml for 210 days. Antibodies against human factor IX were detected at a low level in the serum, although they had no effect on the levels and clotting activity of the expressed factor IX.ConclusionsWe have shown in mouse models that hydrodynamic transfection of pBS‐HCRII‐HP‐FIXA and pBS‐HCRI/II‐HP‐FIXA was able to induce and maintain the expression and clotting activity of human factor IX for a long period of time at a potentially therapeutic level. With an appropriate delivery system, this type of plasmid vector could be clinically useful for the hepatic expression of therapeutic genes including human factor IX. Copyright © 2011 John Wiley & Sons, Ltd.