Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development

Self-amplifying RNA is synthetic nucleic acid engineered to replicate within cells without generating viral particles. Derived from alphavirus genomes, saRNA retains the non-structural elements essential for replication while replacing the structural elements with an antigen of interest. By enabling...

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Main Authors: Thomas Vallet, Marco Vignuzzi
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/17/4/566
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author Thomas Vallet
Marco Vignuzzi
author_facet Thomas Vallet
Marco Vignuzzi
author_sort Thomas Vallet
collection DOAJ
description Self-amplifying RNA is synthetic nucleic acid engineered to replicate within cells without generating viral particles. Derived from alphavirus genomes, saRNA retains the non-structural elements essential for replication while replacing the structural elements with an antigen of interest. By enabling efficient intracellular amplification, saRNA offers a promising alternative to conventional mRNA vaccines, enhancing antigen expression while requiring lower doses. However, this advantage comes with challenges. In this review, we highlight the key limitations of saRNA technology and explore potential strategies to overcome them. By identifying these challenges, we aim to provide insights that can guide the future design of saRNA-based therapeutics, extending their potential beyond vaccine applications.
format Article
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spelling doaj-art-3551b318910941f3b23e11d38d05f3982025-08-20T02:18:11ZengMDPI AGViruses1999-49152025-04-0117456610.3390/v17040566Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine DevelopmentThomas Vallet0Marco Vignuzzi1A*STAR Infectious Diseases Labs (A*IDL), Agency for Science, Technology and Research (A*STAR), Singapore 138634, SingaporeA*STAR Infectious Diseases Labs (A*IDL), Agency for Science, Technology and Research (A*STAR), Singapore 138634, SingaporeSelf-amplifying RNA is synthetic nucleic acid engineered to replicate within cells without generating viral particles. Derived from alphavirus genomes, saRNA retains the non-structural elements essential for replication while replacing the structural elements with an antigen of interest. By enabling efficient intracellular amplification, saRNA offers a promising alternative to conventional mRNA vaccines, enhancing antigen expression while requiring lower doses. However, this advantage comes with challenges. In this review, we highlight the key limitations of saRNA technology and explore potential strategies to overcome them. By identifying these challenges, we aim to provide insights that can guide the future design of saRNA-based therapeutics, extending their potential beyond vaccine applications.https://www.mdpi.com/1999-4915/17/4/566saRNAmRNAvaccinealphaviruslimitationssafety
spellingShingle Thomas Vallet
Marco Vignuzzi
Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
Viruses
saRNA
mRNA
vaccine
alphavirus
limitations
safety
title Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
title_full Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
title_fullStr Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
title_full_unstemmed Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
title_short Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development
title_sort self amplifying rna advantages and challenges of a versatile platform for vaccine development
topic saRNA
mRNA
vaccine
alphavirus
limitations
safety
url https://www.mdpi.com/1999-4915/17/4/566
work_keys_str_mv AT thomasvallet selfamplifyingrnaadvantagesandchallengesofaversatileplatformforvaccinedevelopment
AT marcovignuzzi selfamplifyingrnaadvantagesandchallengesofaversatileplatformforvaccinedevelopment