ArticleNucleic acids research2025
One-pot ligation of multiple mRNA fragments on dsDNA splint advancing regional modification and translation.
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 3 papers.
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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.
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Who cites it
3 citing papers in PubMed.
- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.Pharmaceutics · 2026Review
- Epitranscriptomic Regulation of Hepatitis B Virus by RNA 5-Methylcytosine: Functions, Mechanisms, and Therapeutic Potential.Viruses · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Region-specific RNA modifications are crucial for advancing RNA research and therapeutics, including messenger RNA (mRNA)-based vaccines and immunotherapy. However, the predominant method, synthesizing regionally modified mRNAs with short single-stranded DNA (ssDNA) splints, encounters challenges in ligating long mRNA fragments due to the formation of RNA self-folded complex structures. To address this issue, we developed an efficient strategy using an easily obtained long double-stranded DNA (dsDNA) as a ligation splint after in situ denaturing, while parts of this dsDNA are the templates for transcribing mRNA fragments. We observed that the denatured dsDNA formed a long hybrid duplex with these mRNA fragments, overcoming their structures. Further, our novel strategy remarkably facilitated the ligation of long mRNA fragments (especially structured ones), offering ligation efficiency up to 106-fold higher than the ssDNA method. Using this one-pot strategy, we conveniently synthesized the mRNAs with N1-methylpseudouridine (m1ψ) and 5-methylcytidine (m5C) modifications in specific regions. We have found that compared with the fully modified mRNAs, the 3'UTR m1ψ modifications alone increased the translation efficiency, and the combined modifications of the m1ψ-3'UTR and m5C-5'UTR/CDS exhibited higher translation efficiency and lower immunogenicity in general. Our study presents a broadly applicable strategy for producing regionally modified mRNAs, advancing the potential of mRNA therapeutics.
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Registered trials
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