{"id":"doi:10.3390/v16040503","kind":"review","title":"Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines","authors":["Yıldız A","Răileanu C","Beissert T"],"author_count":3,"year":2024,"published":"2024-03-25","venue":"Viruses","cited_by":23,"doi":"10.3390/v16040503","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3390/v16040503","archive_url":"https://space-kitty.com/papers/doi:10.3390/v16040503","updated":null,"pmid":"38675846","pmcid":"PMC11055088","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11055088/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines\" by Yıldız A, Răileanu C, Beissert T, https://doi.org/10.3390/v16040503, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}