# Circular RNA as a New Vaccine Platform: Considerations, Challenges, and Perspectives

## TL;DR

Circular RNA is being explored as a new vaccine platform due to its stability and ability to trigger strong immune responses for both preventive and cancer vaccines.

## Contribution

The paper reviews circRNA vaccine design strategies and their impact on immunological outcomes in prophylactic and cancer settings.

## Key findings

- circRNA vaccines show sustained antigen availability and robust immune responses.
- circRNA enables multivalent vaccine designs and targeted delivery for effective antibody generation.
- circRNA-based cancer vaccines induce strong CD8+ T cell immunity and support combination immunotherapy.

## Abstract

Circular RNA (circRNA) has emerged as an alternative RNA modality for vaccine development due to its covalently closed structure and enhanced molecular stability compared with linear messenger RNA (mRNA). Following the clinical success of mRNA vaccines, circRNA-based platforms have gained attention in both prophylactic and cancer immunization. Unlike linear mRNA, circRNA relies on cap-independent translation and is commonly produced through in vitro transcription coupled with ribozyme-mediated self-circularization. In prophylactic vaccination, circRNA vaccines have demonstrated sustained antigen availability, robust humoral and cellular immune responses, and flexibility in multivalent designs and targeted delivery strategies that support germinal center reactions and neutralizing antibody generation. In cancer vaccines, circRNA has been applied to tumor-associated antigens, neoantigens, and non-canonical peptides, with a primary focus on inducing potent antigen-specific CD8+ T cell immunity and enabling combination immunotherapy approaches. This review summarizes recent applications of circRNA-based vaccines in prophylactic and cancer settings, emphasizing in vitro transcription-compatible self-circularization strategies and discussing how methodological choices in RNA design, translation control, purification, and delivery shape immunological outcomes.