Gene therapy for the haemophilias.
A variety of approaches for transferring genes for factors VIII and IX are being investigated. No single technique has emerged as superior, but considerable progress has been made in factor expression after in vivo delivery of vectors into animal models, which has led to considerations of clinical trial development for both factors. The last decade has seen several major contributions to the field from many different laboratories. In early attempts coding DNAs (cDNAs) for factor IX or VIII were inserted into cells grown in culture, then the modified cells were returned to the donor animal. Unfortunately, the modified cells expressed clotting factor better in culture (ex vivo) than in the animal (in vivo). This led to attempts to transfer cDNAs by inserting them into vectors that were then administered directly to animals, by either intravenous or intramuscular routes. There was some success with either long-term expression of subtherapeutic amounts of expressed protein or even normal amounts that circulated transiently for up to a few months. However, it has only been within the last year that improved vectors have provided sufficiently encouraging results to allow contemplation of clinical trials in humans. Recent advances that are likely to lead to human clinical trials are summarized in this monograph.
Thompson
A R
AR
University of Washington and the Puget Sound Blood Center, Seattle, USA.
D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000009:adverse effects / Q000592:standards*; D005822:Genetic Vectors / Q000009:adverse effects / Q000592:standards; D006467:Hemophilia A / Q000628:therapy*; D006801:Humans