IN-VIVO GENE-THERAPY OF HEMOPHILIA-B - SUSTAINED PARTIAL CORRECTION IN FACTOR-IX-DEFICIENT DOGS

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which res ults in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B pa tients, preclinical efficacy studies were done in a hemophilia B dog m odel. When the canine factor IX complementary DNA was transduced direc tly into the hepatocytes of affected dogs in vivo, the animals constit utively expressed low levels of canine factor IX for more than 5 month s. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treat ed animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.