ArticleFrontiers in molecular biosciences2018
Structural Components for Amplification of Positive and Negative Strand VEEV Splitzicons.
Article in Frontiers in molecular biosciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
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- A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.International journal of biological sciences · 2024Review
- Trans-Amplifying RNA Vaccines Against Infectious Diseases: A Comparison with Non-Replicating and Self-Amplifying RNA.Methods in molecular biology (Clifton, N.J.) · 2024Article
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- Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets.NPJ vaccines · 2023Article
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- Viral Replicon Systems and Their Biosafety Aspects.Applied biosafety : journal of the American Biological Safety Association · 2023Review
- Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development.Pathogens (Basel, Switzerland) · 2023Review
- Amplifying mRNA vaccines: potential versatile magicians for oncotherapy.Frontiers in immunology · 2023Review
- Self-amplifying mRNA bicistronic influenza vaccines raise cross-reactive immune responses in mice and prevent infection in ferrets.Molecular therapy. Methods & clinical development · 2022Article
- Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.Vaccines · 2022Review
- Self-Amplifying RNA Approach for Protein Replacement Therapy.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA is a promising nucleic acid technology for both vaccines and therapeutics, and replicon RNA has gained traction as a next-generation RNA modality. Replicon RNA self-amplifies using a replicase complex derived from alphaviral non-structural proteins and yields higher protein expression than a similar dose of messenger RNA. Here, we debut RNA splitzicons; a split replicon system wherein the non-structural proteins (NSPs) and the gene of interest are encoded on separate RNA molecules, but still exhibit the self-amplification properties of replicon RNA. We designed both positive and negative strand splitzicons encoding firefly luciferase as a reporter protein to determine which structural components, including the 5' untranslated region (UTR), a 51-nucleotide conserved sequence element (CSE) from the first nonstructural protein, the subgenomic promoter (SGP) and corresponding untranslated region, and an internal ribosomal entry site (IRES) affect amplification. When paired with a NSP construct derived from the whole, wild type replicon, both the positive and negative strand splitzicons were amplified. The combination of the 51nt CSE, subgenomic promoter and untranslated region were imperative for the positive strand splitzicon, while the negative strand was amplified simply with inclusion of the subgenomic promoter. The splitzicons were amplified by NSPs in multiple cell types and show increasing protein expression with increasing doses of NSP. Furthermore, both the positive and negative strand splitzicons continued to amplify over the course of 72 h, up to >100,000-fold. This work demonstrates a system for screening the components required for amplification from the positive and negative strand intermediates of RNA replicons and presents a new approach to RNA replicon technology.
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Registered trials
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.