Hemophilia B has been treated in a pre-clinical model by gene transfer for which deficient clotting factor?

c. Factor IX

 Hemophilia B is a chromosome X-linked blood clotting disorder which results when the gene encoding Factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease have permitted the development of somatic gene therapy protocols aimed at transfer of functional copies of the factor IX gene into the liver. A recombinant retroviral vector was used for the transfer of human factor IX cDNA in rabbit hepatocytes. The infected rabbit hepatocytes produced human factor IX that was indistinguishable from functional protein derived from human plasma.

Factor IX hepatic gene transfer has also been accomplished in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature. Canine factor IX cDNA was transduced directly into the hepatocytes of affected dogs in vivo. The dogs transduced with canine factor IX recombinant retrovirus constitutively expressed canine factor IX for 5 months after the procedure at a high enough concentration to improve the whole blood clotting time and partial thromboplastin time.