ArticleNucleic acids research2025
Characterization of group I introns in generating circular RNAs as vaccines.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Emerging strategies and innovations in circular RNA synthesis.Molecular therapy. Nucleic acids · 2026Review
- Programmable in vivo mRNA circularization for enhanced gene expression in bacteria.Nucleic acids research · 2026Article
- Target site selection and P1 engineering enable highly efficient circular RNA production via end-to-end self-targeting and splicing.Nucleic acids research · 2026Article
- Split intron-exon system for circular RNA synthesis.Nature communications · 2026Article
- Synthetic circRNAs employ IRES activity for translation in cells and in cell-free translation systems.bioRxiv : the preprint server for biology · 2026Article
- Beyond the Sequence: Chemical and Topological Design and Innovations in mRNA Therapeutics.Chemical reviews · 2026Review
- Efficient circRNA Detection Using the Processive Reverse Transcriptase uMRT.Bio-protocol · 2025Article
- Self-splicing RNA circularization facilitated by intact group I and II introns.Nature communications · 2025Article
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Authors and funding
30 authors.
Funding
Abstract
Circular RNAs are an increasingly important class of RNA molecules that can be engineered as RNA vaccines and therapeutics. Here, we screened eight different group I introns for their ability to circularize and delineated different features that are important for their function. First, we identified the Scytalidium dimidiatum group I intron as causing minimal innate immune activation inside cells, underscoring its potential to serve as an effective RNA vaccine without triggering unwanted reactogenicity. Additionally, mechanistic RNA structure analysis was used to identify the P9 domain as important for circularization, showing that swapping sequences can restore pairing to improve the circularization of poor circularizers. We also determined the diversity of sequence requirements for the exon 1 and exon 2 (E1 and E2) domains of different group I introns and engineered a S1 tag within the domains for positive purification of circular RNAs. In addition, this flexibility in E1 and E2 enables substitution with less immunostimulatory sequences to enhance protein production. Our work deepens the understanding of the properties of group I introns, expands the panel of introns that can be used, and improves the manufacturing process to generate circular RNAs for vaccines and therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.