Gene therapy and the hemophilias.

Gene therapy for hemophilia A and B, now in the developmental stage, holds promise of a therapeutic revolution, resulting in amelioration or cure of the hemorrhagic diatheses. The genes for factor VIII and IX have been cloned, and vectors for the transfer of their cDNA into cells have been developed. Although viral and nonviral constructs containing the hemophilia gene have been used, most often modified retroviruses or adenoviruses have been employed. Cells that have been targeted for genetic modification to produce the antihemophilic proteins include hepatocytes, muscle cells, endothelial cells, keratinocytes, and fibroblasts. The delivery system may be (1) ex vivo, with implantation of modified cultured hemophilic cells in the donor, either in tissues or in semipermeable capsules, or (2) in vivo, the vector being delivered directly to target cells, genetically modifying them in situ. Successful in vivo therapy has been demonstrated in a hemophilic animal model, with conversion to a less severe hemophilic state.