Gene therapy and the hemophilias
J. N. Lozier and K. M. Brinkhous
Department of Medicine, University of North Carolina at Chapel Hill 27599.
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.
