Rise of the RNA machines – self-amplification in mRNA vaccine design

Jerome D.G. Comes, Gorben P. Pijlman*, Tessy A.H. Hick

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.

Original languageEnglish
Pages (from-to)1417-1429
JournalTrends in Biotechnology
Issue number11
Early online date14 Jun 2023
Publication statusPublished - Nov 2023


  • lipid nanoparticles
  • mRNA
  • platform technology
  • replicon
  • self-amplifying RNA
  • vaccines


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