Mu, X. et al. An origin of the immunogenicity of in vitro transcribed RNA. Nucleic Acids Res. 46, 5239–5249 (2018).
Google Scholar
Mu, X. & Hur, S. Immunogenicity of in vitro-transcribed RNA. Acc. Chem. Res. 54, 4012–4023 (2021).
Google Scholar
Baiersdörfer, M. et al. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol. Ther. Nucleic Acids 15, 26–35 (2019).
Google Scholar
Moradian, H. et al. Chemical modification of uridine modulates mRNA-mediated proinflammatory and antiviral response in primary human macrophages. Mol. Ther. Nucleic Acids 27, 854–869 (2022).
Google Scholar
Cottrell, K. A. et al. The competitive landscape of the dsRNA world. Mol. Cell 84, 107–119 (2024).
Google Scholar
Pindel, A. & Sadler, A. The role of protein kinase R in the interferon response. J. Interferon Cytokine Res. 31, 59–70 (2011).
Google Scholar
Kim, M. et al. Exogenous RNA surveillance by proton-sensing TRIM25. Science 388, eads4539 (2025).
Google Scholar
Bérouti, M. et al. Pseudouridine RNA avoids immune detection through impaired endolysosomal processing and TLR engagement. Cell 188, 4880–4895 (2025).
Google Scholar
Park, J. et al. Short poly(A) tails are protected from deadenylation by the LARP1–PABP complex. Nat. Struct. Mol. Biol. 30, 330–338 (2023).
Google Scholar
Eisen, T. J. et al. The dynamics of cytoplasmic mRNA metabolism. Mol. Cell 77, 786–799 (2020).
Google Scholar
Lim, J. et al. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell 159, 1365–1376 (2014).
Google Scholar
Norbury, C. J. Cytoplasmic RNA: a case of the tail wagging the dog. Nat. Rev. Mol. Cell Biol. 14, 643–653 (2013).
Google Scholar
Decker, C. J. & Parker, R. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev. 7, 1632–1643 (1993).
Google Scholar
Passmore, L. A. & Coller, J. Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression. Nat. Rev. Mol. Cell Biol. 23, 93–106 (2022).
Google Scholar
Yu, S. & Kim, V. N. A tale of non-canonical tails: gene regulation by post-transcriptional RNA tailing. Nat. Rev. Mol. Cell Biol. 21, 542–556 (2020).
Google Scholar
Warkocki, Z., Liudkovska, V., Gewartowska, O., Mroczek, S. & Dziembowski, A. Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism. Philos. Trans. R. Soc. Lond. B Biol. Sci. 373, 20180162 (2018).
Google Scholar
Lim, J. et al. Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation. Science 361, 701–704 (2018).
Google Scholar
Kim, D. et al. Viral hijacking of the TENT4–ZCCHC14 complex protects viral RNAs via mixed tailing. Nat. Struct. Mol. Biol. 27, 581–588 (2020).
Google Scholar
Seo, J. J. et al. Functional viromic screens uncover regulatory RNA elements. Cell 186, 3291–3306 (2023).
Google Scholar
Li, Y. et al. The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis. Proc. Natl Acad. Sci. USA 119, e2204511119 (2022).
Google Scholar
Mueller, H. et al. PAPD5/7 are host factors that are required for Hepatitis B virus RNA stabilization. Hepatology 69, 1398–1411 (2019).
Google Scholar
Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).
Google Scholar
Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109, 14604–14609 (2012).
Google Scholar
Koch, A. et al. Quantifying the dynamics of IRES and cap translation with single-molecule resolution in live cells. Nat. Struct. Mol. Biol. 27, 1095–1104 (2020).
Google Scholar
Bloom, K., van den Berg, F. & Arbuthnot, P. Self-amplifying RNA vaccines for infectious diseases. Gene Ther. 28, 117–129 (2021).
Google Scholar
Chen, H. et al. Branched chemically modified poly(A) tails enhance the translation capacity of mRNA. Nat. Biotechnol. 43, 194–203 (2025).
Google Scholar
Chen, H. et al. Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation. Nat. Biotechnol. 43, 1128–1143 (2025).
Google Scholar
Fukuchi, K. et al. Internal cap-initiated translation for efficient protein production from circular mRNA. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02561-8 (2025).
Aditham, A. et al. Chemically modified mocRNAs for highly efficient protein expression in mammalian cells. ACS Chem. Biol. 17, 3352–3366 (2022).
Google Scholar
Anhäuser, L. et al. Multiple covalent fluorescence labeling of eukaryotic mRNA at the poly(A) tail enhances translation and can be performed in living cells. Nucleic Acids Res. 47, e42 (2019).
Google Scholar
Strzelecka, D. et al. Phosphodiester modifications in mRNA poly(A) tail prevent deadenylation without compromising protein expression. RNA 26, 1815–1837 (2020).
Google Scholar
Orlandini von Niessen, A. G. et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3′ UTRs identified by cellular library screening. Mol. Ther. 27, 824–836 (2019).
Google Scholar
Leppek, K. et al. Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics. Nat. Commun. 13, 1536 (2022).
Google Scholar
Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).
Google Scholar
Agarwal, V. & Kelley, D. R. The genetic and biochemical determinants of mRNA degradation rates in mammals. Genome Biol. 23, 245 (2022).
Google Scholar
Wang, X. et al. Detection and characterization of a 3′ untranslated region ribonucleoprotein complex associated with human α-globin mRNA stability. Mol. Cell. Biol. 15, 1769–1777 (1995).
Google Scholar
Durrant, M. G. et al. Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome. Nat. Biotechnol. 41, 488–499 (2023).
Google Scholar
Sahin, U. et al. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature 595, 572–577 (2021).
Google Scholar
Wayment-Steele, H. K. et al. RNA secondary structure packages evaluated and improved by high-throughput experiments. Nat. Methods 19, 1234–1242 (2022).
Google Scholar
Hyrina, A. et al. A genome-wide CRISPR screen identifies ZCCHC14 as a host factor required for hepatitis B surface antigen production. Cell Rep. 29, 2970–2978 (2019).
Google Scholar
Mueller, H. et al. A novel orally available small molecule that inhibits Hepatitis B virus expression. J. Hepatol. 68, 412–420 (2018).
Google Scholar
Bazzini, A. A., Lee, M. T. & Giraldez, A. J. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 336, 233–237 (2012).
Google Scholar
Gumińska, N. et al. Direct profiling of non-adenosines in poly(A) tails of endogenous and therapeutic mRNAs with Ninetails. Nat. Commun. 16, 2664 (2025).
Google Scholar
Karikó, K. et al. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
Google Scholar
Li, X. et al. Generation of destabilized green fluorescent protein as a transcription reporter. J. Biol. Chem. 273, 34970–34975 (1998).
Google Scholar
Xia, X. Detailed dissection and critical evaluation of the Pfizer/BioNTech and Moderna mRNA vaccines. Vaccines (Basel) 9, 734 (2021).
Feshchenko, E. et al. Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability. BMC Biotechnol. 12, 77 (2012).
Google Scholar
Zhang, H. et al. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature 621, 396–403 (2023).
Google Scholar
Enuka, Y. et al. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res. 44, 1370–1383 (2016).
Google Scholar
Kristensen, L. S. et al. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet. 20, 675–691 (2019).
Google Scholar
Jens, M. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495, 333–338 (2013).
Google Scholar
Chen, R. et al. Engineering circular RNA for enhanced protein production. Nat. Biotechnol. 41, 262–272 (2023).
Google Scholar
Lorenz, R. et al. ViennaRNA package 2.0. Algorithms Mol. Biol. 6, 26 (2011).
Google Scholar
Huang, L. et al. LinearFold: linear-time approximate RNA folding by 5′-to-3′ dynamic programming and beam search. Bioinformatics 35, i295–i304 (2019).
Google Scholar
Seo, J. J., Jung, S.-J., Lee, S., & Kim, V. N. Virus MPRA—primary screen. Zenodo https://doi.org/10.5281/zenodo.14789418 (2025).
Schoenmaker, L. et al. mRNA–lipid nanoparticle COVID-19 vaccines: structure and stability. Int. J. Pharm. 601, 120586 (2021).
Google Scholar
Ramanathan, M. et al. RNA–protein interaction detection in living cells. Nat. Methods 15, 207–212 (2018).
Google Scholar
Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442–451 (2013).
Google Scholar
van der Toorn, W. et al. Demultiplexing and barcode-specific adaptive sampling for nanopore direct RNA sequencing. Nat. Commun. 16, 3742 (2025).
Google Scholar
Li, H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics 34, 3094–3100 (2018).
Google Scholar
Jung, S.-J., Seo, J., Lee, S., & Kim, V. N. RNA stability enhancers for durable base-modified mRNA therapeutic. Zenodo https://doi.org/10.5281/zenodo.15041853 (2025).
Lee, S. RNA enhancers for durable base-modified mRNA therapeutics. figshare https://doi.org/10.6084/m9.figshare.29614520.v2 (2025).
Chang, H. ChangLabSNU/Jung-2025-DRS: 09-08-2025 (version 20250908). Zenodo https://doi.org/10.5281/zenodo.17077445 (2025)
