{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:03:54Z","timestamp":1790636634645,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v16040503","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:50:49Z","timestamp":1711371049000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines"],"prefix":"10.3390","volume":"16","author":[{"given":"Ay\u015feg\u00fcl","family":"Y\u0131ld\u0131z","sequence":"first","affiliation":[{"name":"TRON\u2014Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"R\u0103ileanu","sequence":"additional","affiliation":[{"name":"TRON\u2014Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-2653","authenticated-orcid":false,"given":"Tim","family":"Beissert","sequence":"additional","affiliation":[{"name":"TRON\u2014Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. 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