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. Rout

Theodora Hatziioannou, Paul D. Bieniasz, John T. Poirier, Margaret R. MacDonald, Volker Thiel^*, Charles M. Rice^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

57 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
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 - 26 Nov 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.abj8430

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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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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.\}",

year = "2021",

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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.

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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VL - 374

SP - 1099

EP - 1106

JO - Science

JF - Science

IS - 6571

ER -

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

Abstract

Bibliographical note

UN SDGs

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