Modification of internal sites of the adenovirus fiber protein and hexon
protein permit effective targeting of adenovirus vectors. Accessible sites to redirect
adenovirus targeting were identified. The HVR5 loop of the hexon protein and the
HI loop of the fiber protein (knob) were highly permissive for the insertion of
foreign protein sequences, which apparently did not impact on the viability and
productivity of corresponding viruses. Accessibility and functionality of the epitope
strongly depend on the size of the neighboring spacers. Other results suggest that
short targeting peptides can be effectively fused to the C-terminus of the fiber
protein. In a specific embodiment, a series of adenovirus vectors modified at the
HVR5 site, the fiber protein HI loop, or the fiber protein C-terminus to target
urokinase-type plasminogen activator receptor bearing cells were prepared. Such
vectors are particularly useful for targeting the vasculature, e.g., for gene therapy
of cancers or cardiovascular conditions.
