Affilin-based retargeting of adenoviral vectors to the epidermal growth factor receptor

•Geneti-chemical capsid-modification with Affilin efficiently retargets adenoviral vectors towards EGFR in vitro•Affilin-decorated vectors are less susceptible to natural sequestration mechanisms•Affilin-decorated vectors exhibit significantly reduced liver tropism after intravenous injection in vivo•Altered off-target vector tropism limits tumor targeting of i.v. injected Affilin-decorated vectors in vivo•Hampered intratumoral EGFR accessibility limits tumor targeting of i.v. injected Affilin-decorated vectors in vivo