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Updated: Oct 16, 2025

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
Published on: June 6, 2025
Replication and single-cycle delivery of SARS-CoV-2 replicons
Inna Ricardo-Lax1, Joseph M Luna1, Tran Thi Nhu Thao2,3,4
1Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Researchers developed a novel yeast-based system to create noninfectious, self-replicating SARS-CoV-2 RNAs. This platform enables safe research into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral development in lower-containment labs.
Area of Science:
- Molecular Virology
- Genetics
- Infectious Diseases
Background:
- Molecular virology tools are essential for studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing therapeutics.
- There is a need for experimental systems that do not require infectious, spread-capable viruses, particularly for use in lower-containment laboratory settings.
Purpose of the Study:
- To develop a safe and versatile experimental system for SARS-CoV-2 research.
- To create noninfectious, self-replicating RNA constructs for SARS-CoV-2 studies.
- To establish a platform for antiviral drug screening and characterization of viral variants.
Main Methods:
- Utilized a yeast-based reverse genetics system.
- Engineered spike-deleted SARS-CoV-2 self-replicating RNAs (replicons).
- Employed trans-complementation with viral glycoproteins to generate replicon delivery particles for single-cycle cell entry.
Main Results:
- Successfully developed noninfectious SARS-CoV-2 replicons.
- Demonstrated the ability to generate replicon delivery particles for versatile cell entry.
- Established a system for single-cycle delivery into various cell types.
Conclusions:
- The developed SARS-CoV-2 replicon system is a convenient and versatile platform.
- This system facilitates antiviral drug screening, neutralization assays, and host factor validation.
- It is also valuable for characterizing emerging SARS-CoV-2 variants in a safe manner.
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