Hemophilia as a model disease for gene therapy of genetic disorders

Abstract

Gene therapy offers the potential for cure of hemophilia, a sex-linked genetic bleeding disorder caused by deficiency of either coagulation factor VIII or coagulation factor IX. The features of hemophilia that make it a leading candidate for gene therapy include the fact that the factor VIII and factor IX genes have been identified and cloned, therapeutic benefit would result from achieving expression at plasma levels as low as 1% of normal, and a wide variety of gene transfer vectors and cell target types could be useful. The challenge is to obtain long-term gene expression at levels sufficient to prevent spontaneous bleeding, while avoiding unwanted toxicity or immune responses to the expressed clotting factor. © 2006 Humana Press Inc.