Summary
The recombinant era for haemophilia began in the early 1980s with the cloning and subsequent expression of functional proteins for both factors VIII and IX. Efficient production of recombinant clotting factors in mammalian cell culture systems required overcoming significant challenges due to the complex post-translational modifications that were integral to their procoagulant function. The quick development and commercialization of recombinant clotting factors was, in part, facilitated by the catastrophic impact of viral contamination of plasma-derived clotting factor concentrates at the time. Since their transition into the clinic, the recombinant versions of both factor VIII and IX have proven to be remarkable facsimiles of their plasma-derived counterparts. The broad adoption of recombinant therapy throughout the developed world has significantly increased the supply of clotting factor concentrates and helped advance aggressive therapeutic interventions such as prophylaxis. The development of recombinant VIIa was a further advance bringing a recombinant option to haemophilia patients with inhibitors. Recombinant DNA technology remains the platform to address ongoing challenges in haemophilia care such as reducing the costs of therapy, increasing the availability to the developing world, and improving the functional properties of these proteins. In turn, the ongoing development of new recombinant clotting factor concentrates is providing alternatives for patients with other inherited bleeding disorders.
Keywords
Recombinant - factor VIII - factor IX - factor VIIa - von Willebrand factor
