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Characterization of group I introns in generating circular RNAs as vaccines

ABSTRACT: Group 1 introns can be utilized for efficient circularization of RNA molecules. However different group 1 introns are known to have different properties, including having different efficiencies of circularization and generating different levels of immune response inside cells (reactogenicity). Here, we investigated generating circular RNAs using permuted intron-exon (PIE) systems of group 1 introns from different organisms. We observed that group 1 intron sequences have variable circularization efficiency that is size dependent and circularize with high accuracy. We also determined the sequence properties of the exon1 and exon2 domains of different group1 introns and showed that we can engineer elements such as S1 tag into this domain for better purification. Structural probing and mutational analysis in group 1 introns and their PIE RNAs showed that structural features in P2 and P9 domains are correlated with circularization efficiency and that swapping sequences can improve circularization efficiency. Lastly, we showed that circular RNAs made by Sd group 1 introns elicit lower amount of reactogenicity and either An or Sd can act as effective RNA vaccines. Our work deepens the understanding of the properties of group 1 introns and their use in circular RNA production and medicine.

ORGANISM(S): synthetic construct

PROVIDER: GSE239954 | GEO | 2025/03/12

REPOSITORIES: GEO

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