F8 and hemophilia A: Even though, in humans, the median protein size is only 375 amino acids long (Grieger and Samulski, 2005), easily fitting into an AAV vector with suitable elements for regulation of expression, several important candidate genes for gene replacement therapies, such as USH2A (Usher syndrome type 2A), F8 (hemophilia A) or DMD (Duchenne muscular dystrophy), are too large.