5/3 capsid-modified HDAd demonstrates increased transduction in mouse tibialis anterior. (A) HDAds HDAd5-luc and HDAd5/3-luc were injected into tibialis anterior, and in vivo luciferase imaging was performed 2 days later. (B) HDAd5/3-luc demonstrated significantly higher transduction compared with wild-type capsid HDAd5-luc as shown by significantly increased in vivo luciferase light emission. (C) Vector cDNA copy number in HDAd5/3-luc–injected muscles was also significantly increased in mice sacrificed 2 days and 6 weeks after injection. mdx mice injected with dystrophin-expressing HDAd5/3-Dys showed stronger expression of dystrophin 6 weeks after injection compared with HDAd5-Dys as shown by western blot (D; lanes 1 and 3, HDAd5/3-Dys–injected; lanes 5 and 7, HDAd5-Dys–injected; lanes 2, 4, 6, and 8, contralateral uninjected muscle; lanes 9 and 10, uninjected wild-type C57 muscles) and immunofluorescences staining (E) of tibialis anterior muscles. n=6 muscles for A–C; n=4 for D and E; error bars: standard error.