Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles

Author:

Syed Abdullah M.12ORCID,Taha Taha Y.3ORCID,Tabata Takako3ORCID,Chen Irene P.34ORCID,Ciling Alison2,Khalid Mir M.3ORCID,Sreekumar Bharath3ORCID,Chen Pei-Yi3ORCID,Hayashi Jennifer M.3ORCID,Soczek Katarzyna M.25ORCID,Ott Melanie236ORCID,Doudna Jennifer A.12578ORCID

Affiliation:

1. Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.

2. Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.

3. Gladstone Institute of Virology, San Francisco, CA, USA.

4. Biomedical Sciences Graduate Program, University of California, San Francisco, CA, USA.

5. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

6. Department of Medicine, University of California San Francisco, CA, USA.

7. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

8. Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.

Abstract

A tool to probe SARS-CoV-2 biology To develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerging variants, it is important to understand the viral biology and the effect of mutations. However, this is challenging because live virus can only be studied in a few laboratories that meet stringent safety standards. Syed et al . describe a virus-like particle (VLP) that comprises the four SARS-CoV-2 structural proteins, but instead of packaging viral RNA, it packages messenger RNA (mRNA) that expresses a reporter protein (see the Perspective by Johnson and Menachery). The amount of reporter expressed in receiver cells depends on the efficiency of packaging and assembly in the producer cells and the efficiency of entry into receiver cells. Mutations in the nucleocapsid protein that are found in more transmissible variants increase mRNA packaging and expression. The VLPs provide a platform for studying the effect of mutations in the structural proteins and for screening therapeutics. —VV

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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