Extracellular vesicles engineered to directly target encephalomyocarditis virus ameliorates multi-organ viremia in a lethal infection model.

The outbreak and prevalence of encephalomyocarditis virus (EMCV) causes significant global mortality and morbidity to the pig industry. Though the current and most effective approach to control EMCV outbreak are done through inactivated vaccines, we have yet to see an effective antiviral agent that directly targets EMCV. Here, we present a molecular therapy consisting of extracellular vesicles (EVs) decorated with EMCV-specific single-chain variable fragment (scFv), engineered on the external loop of the EVS transmembrane domain CD63. These EMCV-scFv enriched EVs directly neutralizes infectious EMCV, thereby inhibiting viral proliferation in vitro. Importantly, we demonstrate that systemic delivery of these EVs reduced multi-organ viremia and clinically rescued EMCV infected mice in vivo. This is the first demonstration of the use of direct acting molecularly engineered EVs to target EMCV infection.