F8 and hemophilia B: In contrast, gene therapy directed at hemophilia A has lagged behind that directed at hemophilia B, largely due to the limitations inherent in the size of the FVIII gene and the structure of FVIII, problems achieving therapeutic levels of the transgenic protein, and cellular immune responses to the capsid of the AAV vector [75] (also identified in trials of therapy for hemophilia B, although to a lesser extent), as well as issues related to the duration and variability of this form of therapy [1,4,6].