Ricardo-Lax, Inna; Luna, Joseph M; Tran, Thi Nhu Thao; Le Pen, Jérémie; Yu, Yingpu; Hoffmann, H-Heinrich; Schneider, William M; Razooky, Brandon S; Fernandez-Martinez, Javier; Schmidt, Fabian; Weisblum, Yiska; Trüeb, Bettina Salome; Berenguer Veiga, Inês; Schmied, Kimberly; Ebert, Nadine; Michailidis, Eleftherios; Peace, Avery; Sánchez-Rivera, Francisco J; Lowe, Scott W; Rout, Michael P; ... (2021). Replication and single-cycle delivery of SARS-CoV-2 replicons. Science, 374(6571), pp. 1099-1106. American Association for the Advancement of Science 10.1126/science.abj8430
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Thiel_Replication_and_single-cycle_delivery_science.abj8430.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview |
Molecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs. These noninfectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate replicon delivery particles for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and viral variant characterization.
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