The recent advances in gene transfer technology have expedited the development of gene
therapy for the treatment of hemophilia A. Three different US Food and Drug Administration-
approved phase I clinical trials had been initiated using different gene therapy approaches
each with their own advantages and limitations. In the first gene therapy trial for hemophilia
A, a non-viral approach was being explored for patients with severe hemophilia A using ex
vivo transfected dermal fibroblast expressing B-domaindeleted factor VIII (BDD-FVIII). There …

Study Design The design of the initial clinical studies of AAV-mediated gene transfer for
hemophilia B was influenced by the very limited clinical experience with AAV vectors at that
time (1999). A handful of patients with cystic fibrosis had received AAV-cystic fibrosis
transmembrane conductance regulator (CFTR) in the maxillary sinus or the respiratory
tract,[12][13] but there was no experience with parenteral delivery of vector. In this setting,
administration to a peripheral site (skeletal muscle) rather than systemically (liver), seemed …