2. Academic Validation
  3. 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.
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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