1. Academic Validation
  2. Replication and single-cycle delivery of SARS-CoV-2 replicons

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

  • Science. 2021 Nov 26;374(6571):1099-1106. doi: 10.1126/science.abj8430.
Inna Ricardo-Lax  # 1 Joseph M Luna  # 1 Tran Thi Nhu Thao 2 3 4 Jérémie Le Pen 1 Yingpu Yu 1 H-Heinrich Hoffmann 1 William M Schneider 1 Brandon S Razooky 1 Javier Fernandez-Martinez 5 Fabian Schmidt 6 Yiska Weisblum 6 Bettina Salome Trüeb 2 3 Inês Berenguer Veiga 2 3 Kimberly Schmied 2 3 Nadine Ebert 2 3 Eleftherios Michailidis 1 Avery Peace 1 Francisco J Sánchez-Rivera 7 Scott W Lowe 7 Michael P Rout 5 Theodora Hatziioannou 6 Paul D Bieniasz 6 John T Poirier 8 Margaret R MacDonald 1 Volker Thiel 2 3 Charles M Rice 1
Affiliations

Affiliations

  • 1 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 2 Institute of Virology and Immunology (IVI), Bern, Switzerland.
  • 3 Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • 4 Graduate School for Biomedical Science, University of Bern, Bern, Switzerland.
  • 5 Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
  • 6 Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • 7 Cancer Biology and Genetics, MSKCC, New York, NY 10065, USA.
  • 8 Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA.
  • # Contributed equally.
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 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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