ArticleNature communications2025
Chemical circularization of in vitro transcribed RNA for exploring circular mRNA design.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Emerging strategies and innovations in circular RNA synthesis.Molecular therapy. Nucleic acids · 2026Review
- Circular Photocaged mRNA for Light-induced Late-stage Activation of Translation.Angewandte Chemie (International ed. in English) · 2026Article
- PRNA (New York, N.Y.) · 2026Article
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.Angewandte Chemie (International ed. in English) · 2026Article
- "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Circular RNA encoding relaxin-2 as a potential therapy for liver fibrosis.Molecular therapy. Nucleic acids · 2026Article
- PolyA tail segmentation improves the stability of the template DNA and increases the translatability of in vitro transcribed mRNA.Nucleic acids research · 2026Article
- Circular nucleic acids at the host-virus interface: from immune modulation to therapeutic innovation.Frontiers in immunology · 2026Review
- Review
- RNA denaturation underlies circular RNA separation.Nucleic acids research · 2025Article
- Roles and Applications of Circular RNA in Virus Infection.International journal of molecular sciences · 2025Review
- Incorporating mRNA therapeutics into biological treatments of hematologic malignancies.Frontiers in immunology · 2025Review
- CircZFR functions in cancer from molecular networks to precision therapy.Frontiers in genetics · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circularization is an important step for therapeutic messenger RNA (mRNA) enhancements. Current enzymatic and ribozymatic-based circularization methods face limitations including sequence constraints, purification challenges, and sub-optimal biological activity. Chemical strategies, while promising, have been restricted to short RNA sequences. Here, we report a method for chemically circularized in vitro transcribed RNAs of various lengths (chem-circRNAs; 35-4000 nt) with circularization efficiencies reaching up to 60%. This approach leverages a 5' ethylenediamine modification and a periodate-oxidized 3' end to drive intramolecular reductive amination. We demonstrate that this method is applicable to various sequences and modification compatible. We report the effective separation methods of chem-circRNAs from their linear precursors. We show that protein-coding chem-circRNAs are translationally active in cells and exhibit increased durability, like enzymatically circularized mRNAs. Furthermore, our method allows incorporation of functional modifications, including endocyclic N7-methylguanosine cap and N1-methylpseudouridine, enabling access to chemically defined translationally active circRNAs for therapeutic applications.
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