ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Mitigating Cellular Dysfunction Through Contaminant Reduction in Synthetic circRNA for High-Efficiency mRNA-Based Cell Reprogramming.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
18 citing papers in PubMed.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- 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
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- Review
- Circular RNA encoding relaxin-2 as a potential therapy for liver fibrosis.Molecular therapy. Nucleic acids · 2026Article
- Review
- The mRNA-Based Innovative Strategy: Progress and Challenges.Nano-micro letters · 2026Review
- Review
- Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.Frontiers in cell and developmental biology · 2026Review
- Circular RNA therapeutics: a new class of long-acting RNA medicines for oncology, immunology, and rare diseases.Frontiers in immunology · 2026Review
- Circular RNA: From non-coding regulators to functional protein encoders.Pharmaceutical science advances · 2025Review
- RNA denaturation underlies circular RNA separation.Nucleic acids research · 2025Article
- The potential and challenges of circular RNA in the development of vaccines and drugs for emerging infectious diseases.Molecular therapy. Nucleic acids · 2025Review
- Self-splicing RNA circularization facilitated by intact group I and II introns.Nature communications · 2025Article
- Exploring the Potential and Advancements of Circular RNA Therapeutics.Exploration (Beijing, China) · 2025Review
- Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection.Vaccines · 2025Review
- Mitigating Cellular Dysfunction Through Contaminant Reduction in Synthetic circRNA for High-Efficiency mRNA-Based Cell Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Synthetic circular RNA (circRNA) holds great promise for biomedical research and therapeutic applications, but impurities introduced during synthesis trigger innate immune responses and significantly compromise its efficacy. In this study, key immunogenic byproducts, including double-stranded RNA, 5' triphosphates from uncircularized RNA, and hydrolyzed RNA fragments, are identified as impairing circRNA functionality via RNA-sensing pathways. To address this, a multi-step purification process is developed that combines enzymatic treatments and cellulose-based filtration to effectively remove these contaminants. This approach significantly reduces immune activation and increases manufacturing yields of circRNA by over 10-fold. The purified circRNA demonstrates exceptional performance in induced pluripotent stem cells (iPSCs) reprogramming, achieving over 300% reprogramming efficiency with just three OSKMLN circRNA transfection treatments. Additionally, the purified circRNA achieves high levels and persistent expression of chimeric antigen receptor (CAR) in T cells with high cytotoxicity against tumor cells, making it a promising candidate for mRNA-based CAR-T cell therapy. These findings establish the purification strategy as a scalable and reliable platform for producing therapeutic-grade RNA, with broad applications in mRNA-based cell reprogramming for regenerative medicine and cancer immunotherapy.
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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.