Problems and prospects in gene therapy for hemophilia.

The aim of gene therapy for hemophilia is the stable introduction and expression of a gene encoding functional blood coagulation factor VIII or IX. Although there are as yet no published studies demonstrating long-term expression of therapeutic levels in large animal models of the disease, there have been several reports over the past year of sustained expression of therapeutic levels of clotting factors in small animals, and some of these strategies are currently being applied to hemophilic dogs. Recent advances include optimized retroviral gene transfer, improved adenoviral vectors for high levels of sustained expression of factor VIII in mice, stable therapeutic levels of factor IX expression in mice after transduction of muscle or liver with adenoassociated virus vector, as well as new nonviral gene delivery strategies. Finally, several important mouse and dog models of hemophilia have been characterized during the past year.