# Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines

Review · Yıldız A, Răileanu C, Beissert T

- Archive id: doi:10.3390/v16040503
- Published: 2024-03-25
- Venue: Viruses
- DOI: https://doi.org/10.3390/v16040503
- PMID: 38675846
- PMCID: PMC11055088
- Citations: 23
- Source URL: https://doi.org/10.3390/v16040503
- PDF: https://europepmc.org/articles/PMC11055088/pdf
- Provenance: europepmc

## Abstract

Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike in vitro transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the presence of RNA-amplifying enzymes known as replicases. We recently demonstrated that this property could enhance immune responses with minimal injected RNA amounts. In saRNA-based vaccines, replicase and antigens are encoded on the same mRNA molecule, resulting in very long RNA sequences, which poses significant challenges in production, delivery, and stability. In taRNA-based vaccines, these challenges can be overcome by splitting the replication system into two parts: one that encodes replicase and the other that encodes a short antigen-encoding RNA called transreplicon. Here, we review the identification and use of transreplicon RNA in alphavirus research, with a focus on the development of novel taRNA technology as a state-of-the art vaccine platform. Additionally, we discuss remaining challenges essential to the clinical application and highlight the potential benefits related to the unique properties of this future vaccine platform.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

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