tetano
Editor, Senior Moderator
Science
. 2021 Oct 14;eabj8430.
doi: 10.1126/science.abj8430. Online ahead of print.
Replication and single-cycle delivery of SARS-CoV-2 replicons
Inna Ricardo-Lax[SUP] #[/SUP][SUP] 1 [/SUP], Joseph M Luna[SUP] #[/SUP][SUP] 1 [/SUP], Tran Thi Nhu Thao[SUP] 2 3 4 [/SUP], Jérémie Le Pen[SUP] 1 [/SUP], Yingpu Yu[SUP] 1 [/SUP], H-Heinrich Hoffmann[SUP] 1 [/SUP], William M Schneider[SUP] 1 [/SUP], Brandon S Razooky[SUP] 1 [/SUP], Javier Fernandez-Martinez[SUP] 5 [/SUP], Fabian Schmidt[SUP] 6 [/SUP], Yiska Weisblum[SUP] 6 [/SUP], Bettina Salome Trüeb[SUP] 2 3 [/SUP], Inês Berenguer Veiga[SUP] 2 3 [/SUP], Kimberly Schmied[SUP] 2 3 [/SUP], Nadine Ebert[SUP] 2 3 [/SUP], Eleftherios Michailidis[SUP] 1 [/SUP], Avery Peace[SUP] 1 [/SUP], Francisco J Sánchez-Rivera[SUP] 7 [/SUP], Scott W Lowe[SUP] 7 [/SUP], Michael P Rout[SUP] 5 [/SUP], Theodora Hatziioannou[SUP] 6 [/SUP], Paul D Bieniasz[SUP] 6 [/SUP], John T Poirier[SUP] 8 [/SUP], Margaret R MacDonald[SUP] 1 [/SUP], Volker Thiel[SUP] 2 3 [/SUP], Charles M Rice[SUP] 1 [/SUP]
Affiliations
Abstract
Molecular virology tools are critical for basic studies of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. There remains a need for experimental systems that do not rely on viruses capable of spread that could potentially be used in lower containment settings. Here, we develop spike-deleted SARS-CoV-2 self-replicating RNAs using a yeast-based reverse genetics system. These non-infectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate Replicon Delivery Particles (RDPs) 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 characterizing viral variants.
. 2021 Oct 14;eabj8430.
doi: 10.1126/science.abj8430. Online ahead of print.
Replication and single-cycle delivery of SARS-CoV-2 replicons
Inna Ricardo-Lax[SUP] #[/SUP][SUP] 1 [/SUP], Joseph M Luna[SUP] #[/SUP][SUP] 1 [/SUP], Tran Thi Nhu Thao[SUP] 2 3 4 [/SUP], Jérémie Le Pen[SUP] 1 [/SUP], Yingpu Yu[SUP] 1 [/SUP], H-Heinrich Hoffmann[SUP] 1 [/SUP], William M Schneider[SUP] 1 [/SUP], Brandon S Razooky[SUP] 1 [/SUP], Javier Fernandez-Martinez[SUP] 5 [/SUP], Fabian Schmidt[SUP] 6 [/SUP], Yiska Weisblum[SUP] 6 [/SUP], Bettina Salome Trüeb[SUP] 2 3 [/SUP], Inês Berenguer Veiga[SUP] 2 3 [/SUP], Kimberly Schmied[SUP] 2 3 [/SUP], Nadine Ebert[SUP] 2 3 [/SUP], Eleftherios Michailidis[SUP] 1 [/SUP], Avery Peace[SUP] 1 [/SUP], Francisco J Sánchez-Rivera[SUP] 7 [/SUP], Scott W Lowe[SUP] 7 [/SUP], Michael P Rout[SUP] 5 [/SUP], Theodora Hatziioannou[SUP] 6 [/SUP], Paul D Bieniasz[SUP] 6 [/SUP], John T Poirier[SUP] 8 [/SUP], Margaret R MacDonald[SUP] 1 [/SUP], Volker Thiel[SUP] 2 3 [/SUP], Charles M Rice[SUP] 1 [/SUP]
Affiliations
- PMID: 34648371
- DOI: 10.1126/science.abj8430
Abstract
Molecular virology tools are critical for basic studies of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. There remains a need for experimental systems that do not rely on viruses capable of spread that could potentially be used in lower containment settings. Here, we develop spike-deleted SARS-CoV-2 self-replicating RNAs using a yeast-based reverse genetics system. These non-infectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate Replicon Delivery Particles (RDPs) 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 characterizing viral variants.