Bioengineered molecules for the management of haemophilia: Promise and remaining challenges

Recombinant DNA technology has led to accelerating introduction of novel therapeutics for the treatment of haemophilia. This technology has driven the development of recombinant clotting factors, extended half-life clotting factors, alternative biologics to promote haemostasis and enabled the launch of the gene therapy era for haemophilia. At the core of this technology is the ability to study the structure and function of the native molecules and to apply rational bioengineering to overcome limitations to the existing therapies. Through the study of haemophilia-causing mutations, site-directed mutagenesis, detailed structural models and a wide repertoire of animal models, new bioengineering strategies are helping overcome some of the remaining limitations and challenges of traditional clotting factor concentrates. Some of these bioengineering strategies are now being partnered with improvements in vectorology leading to the first wave of successful gene therapy approaches. This study will review past and present bioengineered molecules that are advancing care for haemophilia as well as novel approaches that promise to continue to improve care and outcomes for patients with haemophilia.