Factoring nonviral gene therapy into a cure for hemophilia A.
Gene therapy for hemophilia A has fallen short of success despite several clinical trials conducted over the past decade. Challenges to its success include vector immunogenicity, insufficient transgene expression levels of Factor VIII, and inhibitor antibody formation. Gene therapy has been dominated by the use of viral vectors, as well as the immunogenic and oncogenic concerns that accompany these strategies. Because of the complexity of viral vectors, the development of nonviral DNA delivery methods may provide an efficient and safe alternative for the treatment of hemophilia A. New types of nonviral strategies, such as DNA integrating vectors, and the success of several nonviral animal studies, suggest that nonviral gene therapy has curative potential and justifies its clinical development.
Gabrovsky
Vanessa
V
Stanford University School of Medicine, Department of Genetics, Stanford, CA 94305-5120, USA.
Calos
Michele P
MP
D002986:Clinical Trials as Topic; D005169:Factor VIII / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D005822:Genetic Vectors; D006467:Hemophilia A / Q000235:genetics / Q000628:therapy*; D006801:Humans; D019076:Transgenes
D005169:Factor VIII