Gene therapy for haemophilia: the end of a 'royal pathology' in the third millennium?

Haemophilia is an ideal condition for gene therapy because of its monogenetic character and the fact that it requires only a small amount of the expressed protein to achieve palliation. To date, research in the field of gene therapy for haemophilia has largely relied on retroviruses, adenoviruses and adeno-associated viruses as transfer vectors and the major aims will be to achieve stable longlasting in vivo expression of factors VIII or IX (FVIII or FIX) at therapeutic levels. Two clinical trials have been approved by the US Food and Drug Administration (FDA), using miniadenovirus FVIII and the intrahepatic and intramuscular delivery of adeno-associated virus FIX. In the third millennium, haemophilia treatment should encompass more ambitious goals through gene replacement, to result in permanent and safe haemophilia 'eradication', making haemophilia a part of the history of medicine.