Rational Design of a Replication‐Competent and Inheritable Magnetic Viruses for Targeting Biomedical Applications

Abstract Infection with live‐attenuated vaccines always inevitably induces side effects that reduce their safety. This study suggests a concept of magnetic virus produced by genetically modifying viral surfaces with Fe₃O₄ nanoparticles (NPs) to control their tropisms. An iron‐affinity peptide is designed to be displayed on the viral surface protein (VP1) of human enterovirus type 71 (EV71), a typical nonenveloped picornavirus, as the model. The modified EV71 can self‐bind with Fe₃O₄ NPs under physiological conditions, resulting in novel EV71‐Fe₃O₄ hybrid materials. This rationally engineered EV71 with Fe₃O₄ retains its original biological infectivity, but its tropism can be precisely controlled by magnetism. Both in vitro and in vivo experiments demonstrate that EV71‐Fe₃O₄ can infect only a desired area within the limit of the applied magnetic field, which effectively reduces its pathological damage. More importantly, this characteristic of EV71 can be inherited due to the gene‐induced coassembly of viruses and NPs. This achievement provides a proof of concept in virus vaccine improvement by a combination of gene modification and material incorporation, leading to great potential for biomedical developments.