ArticleProceedings of the National Academy of Sciences of the United States of America2014
Enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic RNAs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
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- Building better mRNA for therapeutics.Nature biotechnology · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development.Viruses · 2025Review
- A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- mRNA medicine: Recent progresses in chemical modification, design, and engineering.Nano research · 2024Article
- A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.International journal of biological sciences · 2024Review
- Alphavirus-based replicons demonstrate different interactions with host cells and can be optimized to increase protein expression.Journal of virology · 2023Article
- Messenger RNA-Based Therapeutics and Vaccines: What's beyond COVID-19?ACS pharmacology & translational science · 2023Review
- Review
- Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2.Molecular therapy. Nucleic acids · 2023Article
- Vaccinations in pregnancy against TORCH pathogens.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Construction of a mini-RNA replicon inSynthetic biology (Oxford, England) · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Since the development of infectious cDNA clones of viral RNA genomes and the means of delivery of the in vitro-synthesized RNA into cells, alphaviruses have become an attractive system for expression of heterologous genetic information. Alphaviruses replicate exclusively in the cytoplasm, and their genetic material cannot recombine with cellular DNA. Alphavirus genome-based, self-replicating RNAs (replicons) are widely used vectors for expression of heterologous proteins. Their current design relies on replacement of structural genes, encoded by subgenomic RNAs (SG RNA), with heterologous sequences of interest. The SG RNA is transcribed from a promoter located in the alphavirus-specific RNA replication intermediate and is not further amplified. In this study, we have applied the accumulated knowledge of the mechanism of alphavirus replication and promoter structures, in particular, to increase the expression level of heterologous proteins from Venezuelan equine encephalitis virus (VEEV)-based replicons. During VEEV infection, replication enzymes are produced in excess to RNA replication intermediates, and a large fraction of them are not involved in RNA synthesis. The newly designed constructs encode SG RNAs, which are not only transcribed from the SG promoter, but are additionally amplified by the previously underused VEEV replication enzymes. These replicons produce SG RNAs and encoded proteins of interest 10- to 50-fold more efficiently than those using a traditional design. A modified replicon encoding West Nile virus (WNV) premembrane and envelope proteins efficiently produced subviral particles and, after a single immunization, elicited high titers of neutralizing antibodies, which protected mice from lethal challenge with WNV.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.