Hepatic gene therapy for hemophilia B
A number of different cell types including keratinocytes, hepatodytes, fibroblasts, myoblasts, and endothelial cells have been targeted for factor IX (RIX) gene replacement therapy.1–7 Following gene transfer, these cells have produced functional RIX because of their ability to gamma-carboxylate the appropriate “gla” domains and secrete the functional protein. Most efforts to date have employed an ex vivo gene transfer method in rodents and involve transfer of the F.IX gene into the cells via a recombinant retroviral vector and subsequent transplantation of the cells back into the animal. Two major problems encountered in these studies have been the rather low concentration of circulating F.IX and/or the loss of F.IX expression over time. The inability to achieve long-term expression is primarily the result of loss of the transduced cells or inactivation of the expression vectors.
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- 13.Evans, J.P., Brinkhous, K.M., Brayer, G.D., Reisner, H.M., High, K.A. Proc. Natl. Acad. Sci., USA. 86:10095–10099.Google Scholar