ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
A trans-amplifying RNA simplified to essential elements is highly replicative and robustly immunogenic in mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
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- The mRNA-Based Innovative Strategy: Progress and Challenges.Nano-micro letters · 2026Review
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Endo/Lysosomal-Escapable Lipid Nanoparticle Platforms for Enhancing mRNA Delivery in Cancer Therapy.Pharmaceutics · 2025Review
- Trans amplifying mRNA vaccine expressing consensus spike elicits broad neutralization of SARS CoV 2 variants.NPJ vaccines · 2025Article
- Promising Vaccine Formulations for Emerging Infectious Diseases.International journal of molecular sciences · 2025Review
- Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- mRNA vaccines as cancer therapies.Chinese medical journal · 2024Review
- mRNA vaccines for infectious diseases - advances, challenges and opportunities.Nature reviews. Drug discovery · 2024Review
- 1mΨ influences the performance of various positive-stranded RNA virus-based replicons.Scientific reports · 2024Article
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Corrections and comments
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- Erratum issued
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trans-amplifying RNA (taRNA) is a split-vector derivative of self-amplifying RNA (saRNA) and a promising vaccine platform. taRNA combines a non-replicating mRNA encoding an alphaviral replicase and a transreplicon (TR) RNA coding for the antigen. Upon translation, the replicase amplifies the antigen-coding TR, thereby requiring minimal amounts of TR for immunization. TR amplification by the replicase follows a complex mechanism orchestrated by genomic and subgenomic promoters (SGPs) and generates genomic and subgenomic amplicons whereby only the latter are translated into therapeutic proteins. This complexity merits simplification to improve the platform. Here, we eliminated the SGP and redesigned the 5' untranslated region to shorten the TR (STR), thereby enabling translation of the remaining genomic amplicon. We then applied a directed evolution approach to select for faster replicating STRs. The resulting evolved STR (eSTR) had acquired A-rich 5' extensions, which improved taRNA expression thanks to accelerated replication. Consequently, we reduced the minimal required TR amount by more than 10-fold without losing taRNA expression in vitro. Accordingly, eSTR-immunized mice developed greater antibody titers to taRNA-encoded influenza HA than TR-immunized mice. In summary, this work points the way for further optimization of taRNA by combining rational design and directed evolution.
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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.