HEPATIC GENE-THERAPY FOR HEMOPHILIA-B

Early retroviral-mediated factor IX gene transfer into deficient dogs showed that constitutive expression of low levels of factor IX which h as led to persistent improvement of clinically relevant parameters suc h as the WBCT and PTT. Conversely, in vivo adenoviral mediated deliver y of the factor IX cDNA into hepatocytes of haemophilia B dogs has res ulted in greater than wild-type plasma concentrations of clotting fact or with complete, albeit transient normalization of haemostasis for a short time. An immune response directed against the vector transduced cells presented a big obstacle to clinical application. However, the f uture of gene therapy for factor IX deficiency appears bright with the development of fully adenoviral-gene deleted vectors, rAAV and lentiv iral vectors which seem to offer safety, therapeutic levels of factor IX and relatively long-term persistence. We must proceed with cautious optimism as these vector systems undergo further scrutiny.