Fig. 10.

Overview of subsequent modifications for the generation of a new gene vector. Depicted are subsequent steps of engineering. Based on a wild-type HAdV5, which binds FX and e.g. upon intravenous administration this leads to very strong liver tropism. The viral capsid was genetically engineered to ablate the FX interaction. A retargeting adapter allows specific transduction of cancer cells via cell surface markers such as EGFR or HER2. Without the FX coat, the viral capsid can easily be destroyed by the immune system, e.g., by ADIN. We generated a novel artificial shield based on hexon-binding proteins and the viral capsid symmetry determined by EM and crystal structures. The retargeted shielded virus was tested for neutralization, e.g., by ADIN, and for increased gene delivery to the tumor compared to the liver, described as the tumor-to-liver ratio, in both EGFR- and HER2-overexpressing in vivo tumor models