Genetically engineered MRI-trackable extracellular vesicles as SARS-CoV-2 mimetics for examination of viral binding
2Department of Biological Sciences, Weizmann Institute of Science
The elucidation of viral-receptor interactions and an understanding of virus-spreading mechanisms are of great importance, particularly in the era of a pandemic. The hazards of the infectiousness of viruses, their rapid mutagenesis, and the need to study viral-receptor interactions in a complex in vivo setup call for new imaging platforms to shed light on complex host-pathogens interactions. Relying on previous evidences showing that the receptor binding domain (RBD) of SARS-CoV-2 interact with the cellular ACE2 receptor during COVID19 contamination, we developed a biocompatible genetically engineered extracellular vesicles (EVs) that display the RBD of SARS-CoV-2 on their surface as coronavirus mimetics (EVs-RBD). Loading EVs-RBD with iron oxide nanoparticles makes them MRI-visible and, thus, allows mapping of the binding of RBD to ACE2 receptors noninvasively in live subjects. Indeed, RBD -ACE2 interaction was confirmed by the higher accumulation of EVsRBD in ACE2-expressing cells compared to control EVsnoRBD. Moreover, we show that EVsRBD can be modified to display mutants of the RBD of SARS-CoV-2, allowing rapid screening of currently raised or predicted variants of the virus, or mimic other type of viruses in the future.
To conclude, the proposed platform (ACS Nano 2022, 16, 8, 12276–12289) shows relevance and cruciality in the examination of quickly evolving pathogenic viruses in an adjustable, fast, and safe manner. Relying on MRI for visualization, the presented approach could be considered in the future to non-invasively map ligand-receptor binding events in deep tissues, which are not accessible to luminescence-based imaging.