In vitro characterization of engineered red blood cells as viral traps against HIV-1 and SARS-CoV-2

Engineered red blood cells (RBCs) expressing viral receptors could be used therapeutically as traps, RBCs lack nuclei and other organelles required for replication. However, expression of on is difficult to achieve since mature erythrocytes the cellular machinery synthesize proteins. Herein, we show that combination a powerful erythroid-specific system transgene codon optimization yields high levels HIV-1 CD4 CCR5, well CD4-glycophorin A (CD4-GpA) fusion protein in erythroid progenitor cells, which efficiently differentiated into enucleated RBCs. entered co-expressed but entry was not neutralization, or CD4-GpA absence CCR5 sufficient potently neutralize prevent infection CD4+ T vitro due formation high-avidity interactions with trimeric Env spikes virions. To facilitate continuous large-scale production RBC generated erythroblast cell lines stably ACE2-GpA proteins, produced potent traps against SARS-CoV-2. 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