ArticleMolecular therapy. Nucleic acids2025
Development and comprehensive evaluation of scarless circularization systems for circular RNA therapeutics.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Self-amplifying RNA (saRNA) and circular RNA (circRNA) vaccines: Progress, evidence gaps, and translational pathways for durable and scalable immunization.Human vaccines & immunotherapeutics · 2026Review
- A scalable platform for dumbbell siRNA production using engineeredMolecular therapy. Nucleic acids · 2026Article
- Research Progress, Application, and Industrialization Prospects of Circular RNA Vaccines in Viral Diseases.Vaccines · 2026Review
- Generation of precise and accurate engineered circRNAs using enzymatic ligation.Nucleic acids research · 2026Article
- Circular RNA as a New Vaccine Platform: Considerations, Challenges, and Perspectives.Vaccines · 2026Review
- Circular RNA therapeutics: a new class of long-acting RNA medicines for oncology, immunology, and rare diseases.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circular RNAs (circRNAs) are promising candidates for RNA-based therapeutics due to their enhanced stability and sustained protein production compared to linear mRNAs. Traditional circRNA production methods, such as the Anabaena-based permuted intron-exon (Ana-PIE) system, often introduce extraneous sequences, referred to as "scars." However, a comprehensive evaluation of the functional consequences of incorporating or omitting extraneous "scar" sequences during circRNA production is lacking. In this study, we developed two scarless circRNA circularization systems, SCAP and mSCAP, based on Ana-PIE. We systematically compared these systems, along with the scarless Clean-PIE approach, across key performance metrics: circularization efficiency, protein production, stability, and immunogenicity. By quantifying these parameters using multiple reporter genes, we provide a comprehensive evaluation demonstrating that removing scar sequences, particularly with the SCAP system, can enhance protein production while preserving stability and maintaining minimal immunogenicity. Our comprehensive evaluation establishes a framework for the rational design of circRNA 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.