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Updated: Mar 29, 2026

Large-scale Production of Recombinant RNAs on a Circular Scaffold Using a Viroid-derived System in Escherichia coli
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Circular RNA as a New Vaccine Platform: Considerations, Challenges, and Perspectives.

Kyung Hyun Lee1, Jaejin Lee1, Seong-Wook Lee1,2

  • 1R&D Center, Rznomics Inc., Seongnam 13486, Republic of Korea.

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Summary

Circular RNA (circRNA) vaccines offer enhanced stability and potent immune responses for both prophylactic and cancer immunization. Their unique structure enables cap-independent translation, driving robust cellular and humoral immunity.

Keywords:
RNA vaccinecancer vaccinecap-independent translationcircular RNApreventive vaccineprophylactic vaccineself-circularization

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Area of Science:

  • Biotechnology
  • Immunology
  • Molecular Biology

Background:

  • Circular RNA (circRNA) presents a stable alternative to linear messenger RNA (mRNA) for vaccine development.
  • The success of mRNA vaccines has spurred interest in circRNA platforms for prophylactic and cancer immunization.
  • circRNA utilizes cap-independent translation and is produced via in vitro transcription with self-circularization.

Purpose of the Study:

  • To review recent advancements in circRNA-based vaccine applications for prophylactic and cancer settings.
  • To highlight in vitro transcription-compatible self-circularization strategies for circRNA production.
  • To discuss how design, translation, purification, and delivery methods influence immunological outcomes.

Main Methods:

  • Review of current literature on circRNA vaccine development and application.
  • Analysis of self-circularization techniques for in vitro transcription-compatible circRNA synthesis.
  • Examination of factors affecting circRNA vaccine efficacy, including design, translation, purification, and delivery.

Main Results:

  • circRNA vaccines demonstrate sustained antigen presentation and elicit strong humoral and cellular immune responses.
  • In prophylactic settings, circRNA supports germinal center reactions and neutralizing antibody generation.
  • In cancer vaccines, circRNA effectively induces CD8+ T cell immunity and facilitates combination immunotherapy.

Conclusions:

  • circRNA technology offers a promising platform for developing next-generation vaccines.
  • Methodological choices in circRNA vaccine development significantly impact immunological effectiveness.
  • Further research into circRNA design, production, and delivery will optimize its potential in vaccination.