Replication and single-cycle delivery of SARS-CoV-2 replicons

Inna Ricardo-Lax; Joseph M. Luna; Tran Thi Nhu Thao; Jérémie Le Pen; Yingpu Yu; H. Heinrich Hoffmann; William M. Schneider; Brandon S. Razooky; Javier Fernandez-Martinez; Fabian Schmidt; Yiska Weisblum; Bettina Salome Trüeb; Inês Berenguer Veiga; Kimberly Schmied; Nadine Ebert; Eleftherios Michailidis; Avery Peace; Francisco J. Sánchez-Rivera; Scott W. Lowe; Michael P. Rout; Theodora Hatziioannou; Paul D. Bieniasz; John T. Poirier; Margaret R. MacDonald; Volker Thiel; Charles M. Rice

doi:10.1126/science.abj8430

Replication and single-cycle delivery of SARS-CoV-2 replicons

Inna Ricardo-Lax, Joseph M. Luna, Tran Thi Nhu Thao, Jérémie Le Pen, Yingpu Yu, H. Heinrich Hoffmann, William M. Schneider, Brandon S. Razooky, Javier Fernandez-Martinez, Fabian Schmidt, Yiska Weisblum, Bettina Salome Trüeb, Inês Berenguer Veiga, Kimberly Schmied, Nadine Ebert, Eleftherios Michailidis, Avery Peace, Francisco J. Sánchez-Rivera, Scott W. Lowe, Michael P. RoutTheodora Hatziioannou, Paul D. Bieniasz, John T. Poirier, Margaret R. MacDonald, Volker Thiel, Charles M. Rice

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43 Scopus citations

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. 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 transcomplemented 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.

Original language	English (US)
Pages (from-to)	1099-1106
Number of pages	8
Journal	Science
Volume	374
Issue number	6571
DOIs	https://doi.org/10.1126/science.abj8430
State	Published - Nov 26 2021
Externally published	Yes

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Ricardo-Lax, I., Luna, J. M., Thao, T. T. N., Le Pen, J., Yu, Y., Hoffmann, H. H., Schneider, W. M., Razooky, B. S., Fernandez-Martinez, J., Schmidt, F., Weisblum, Y., Trüeb, B. S., Veiga, I. B., Schmied, K., Ebert, N., Michailidis, E., Peace, A., Sánchez-Rivera, F. J., Lowe, S. W., ... Rice, C. M. (2021). Replication and single-cycle delivery of SARS-CoV-2 replicons. Science, 374(6571), 1099-1106. https://doi.org/10.1126/science.abj8430

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title = "Replication and single-cycle delivery of SARS-CoV-2 replicons",

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. 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 transcomplemented 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.",

author = "Inna Ricardo-Lax and Luna, {Joseph M.} and Thao, {Tran Thi Nhu} and {Le Pen}, J{\'e}r{\'e}mie and Yingpu Yu and Hoffmann, {H. Heinrich} and Schneider, {William M.} and Razooky, {Brandon S.} and Javier Fernandez-Martinez and Fabian Schmidt and Yiska Weisblum and Tr{\"u}eb, {Bettina Salome} and Veiga, {In{\^e}s Berenguer} and Kimberly Schmied and Nadine Ebert and Eleftherios Michailidis and Avery Peace and S{\'a}nchez-Rivera, {Francisco J.} and Lowe, {Scott W.} and Rout, {Michael P.} and Theodora Hatziioannou and Bieniasz, {Paul D.} and Poirier, {John T.} and MacDonald, {Margaret R.} and Volker Thiel and Rice, {Charles M.}",

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year = "2021",

month = nov,

day = "26",

doi = "10.1126/science.abj8430",

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Ricardo-Lax, I, Luna, JM, Thao, TTN, Le Pen, J, Yu, Y, Hoffmann, HH, Schneider, WM, Razooky, BS, Fernandez-Martinez, J, Schmidt, F, Weisblum, Y, Trüeb, BS, Veiga, IB, Schmied, K, Ebert, N, Michailidis, E, Peace, A, Sánchez-Rivera, FJ, Lowe, SW, Rout, MP, Hatziioannou, T, Bieniasz, PD, Poirier, JT, MacDonald, MR, Thiel, V & Rice, CM 2021, 'Replication and single-cycle delivery of SARS-CoV-2 replicons', Science, vol. 374, no. 6571, pp. 1099-1106. https://doi.org/10.1126/science.abj8430

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T1 - Replication and single-cycle delivery of SARS-CoV-2 replicons

AU - Ricardo-Lax, Inna

AU - Luna, Joseph M.

AU - Thao, Tran Thi Nhu

AU - Le Pen, Jérémie

AU - Yu, Yingpu

AU - Hoffmann, H. Heinrich

AU - Schneider, William M.

AU - Razooky, Brandon S.

AU - Fernandez-Martinez, Javier

AU - Schmidt, Fabian

AU - Weisblum, Yiska

AU - Trüeb, Bettina Salome

AU - Veiga, Inês Berenguer

AU - Schmied, Kimberly

AU - Ebert, Nadine

AU - Michailidis, Eleftherios

AU - Peace, Avery

AU - Sánchez-Rivera, Francisco J.

AU - Lowe, Scott W.

AU - Rout, Michael P.

AU - Hatziioannou, Theodora

AU - Bieniasz, Paul D.

AU - Poirier, John T.

AU - MacDonald, Margaret R.

AU - Thiel, Volker

AU - Rice, Charles M.

N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15

PY - 2021/11/26

Y1 - 2021/11/26

N2 - 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 transcomplemented 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.

AB - 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 transcomplemented 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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DO - 10.1126/science.abj8430

M3 - Article

SN - 1095-9203

VL - 374

SP - 1099

EP - 1106

JO - Science

JF - Science

IS - 6571

ER -

Replication and single-cycle delivery of SARS-CoV-2 replicons

Abstract

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