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

作者：Kim Hong Sung; Kim Jong Chul; Lee Yeon Kyung; Kim Jung Seok; Park Yong Serk^*

来源：Journal of Gene Medicine, 2011, 13(7-8): 365-372.

DOI：10.1002/jgm.1583

• factor IX
• hemophilia B
• hepatic control region
• hydrodynamic gene transfection

Background Long-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.
Methods HCR 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.
Results HCR 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 500ng/ml for 210days. 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.
Conclusions We 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.

• 出版日期2011-8