Enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic RNAs
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Significance: One of the goals of modern molecular medicine is delivery and expression of heterologous genes in living organisms. RNA-based delivery vectors are a safer choice than DNA vectors, but they are prone to degradation and are highly dependent on efficient delivery methods. One of the ways to improve RNA vector performance is to increase the level of expression of the encoded proteins. We followed this approach and modified standard alphavirus replicon-based expression systems to make the transcribed subgenomic RNA additionally amplifiable by viral replication enzymes. Higher levels of subgenomic RNA synthesis increased the replicons’ expression efficiency at least 10-fold. Such replicons can be widely applied for development of efficient DNA and RNA vaccines and protein production in vitro.
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saRNA vaccines can deliver genetic information encoding the target antigen and other genes, e.g., viral RNA polymerase, to enable mRNA to self-replicate.
“saRNA vaccines can deliver genetic information encoding the target antigen and other genes, e.g., viral RNA polymerase, to enable mRNA to self-replicate.109,110”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [110]
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- Authors
- Kim, D. Y., Atasheva, S., McAuley, A. J., Plante, J. A., Frolova, E. I., Beasley, D. W. C., & Frolov, I.
- Affiliations
- University of Alabama at Birmingham (US)
- Department of Microbiology and Immunology,
- Department of Pathology, and
- The University of Texas Medical Branch at Galveston (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-07-07
- Volume
- 111
- Issue
- 29
- Pages
- 10708-10713
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4115546
- OpenAlex
- W1987728748
- Cited by
- 57
- References
- 40
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 3
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI073301, R01AI070207, R01AI095449, T32AI060549)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- alphavirus replicon, Venezuelan equine encephalitis virus, West Nile virus, heterologous expression, subgenomic promoter, subviral particles, neutralizing antibodies, live attenuated vaccine, mouse protection
- MeSH terms
- Alphavirus, Animals, Encephalitis Virus, Venezuelan Equine, Genetic Vectors, Replicon, RNA, Viral, Protein Biosynthesis, Viral Proteins, Virus Replication, West Nile virus, Gene Expression, Genome, Viral, Interferon-beta, RNA Interference, Intracellular Space, Green Fluorescent Proteins, Mice, Antibodies, Neutralizing
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