Current status of haemophilia gene therapy

Summary After many reports of successful gene therapy studies in small and large animal models of haemophilia, we have, at last, seen the first signs of success in human patients. These very encouraging results have been achieved with the use of adeno‐associated viral (AAV) vectors in patients with severe haemophilia B. Following on from these initial promising studies, there are now three ongoing trials of AAV‐mediated gene transfer in haemophilia B all aiming to express the factor IX gene from the liver. Nevertheless, as discussed in the first section of this article, there are still a number of significant hurdles to overcome if haemophilia B gene therapy is to become more widely available. The second section of this article deals with the challenges relating to factor VIII gene transfer. While the recent results in haemophilia B are extremely encouraging, there is, as yet, no similar data for factor VIII gene therapy. It is widely accepted that this therapeutic target will be significantly more problematic for a variety of reasons including accommodating the larger factor VIII cDNA, achieving adequate levels of transgene expression and preventing the far more frequent complication of antifactor VIII immunity. In the final section of the article, the alternative approach of lentiviral vector‐mediated gene transfer is discussed. While AAV‐mediated approaches to transgene delivery have led the way in clinical haemophilia gene therapy, there are still a number of potential advantages of using an alternative delivery vehicle including the fact that ex vivo host cell transduction will avoid the likelihood of immune responses to the vector. Overall, these are exciting times for haemophilia gene therapy with the likelihood of further clinical successes in the near future.