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
  • 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.
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. 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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