ArticleNucleic acids research2024
Trinucleotide cap analogs with triphosphate chain modifications: synthesis, properties, and evaluation as mRNA capping reagents.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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
7 citing papers in PubMed.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Thio-modification effects on mRNA translation using a PureCap-based capping method.RSC chemical biology · 2026Article
- The trypanosome mRNA decapping enzyme ALPH1 prefers caps without m7G methylation and produces diphosphate RNA.Nucleic acids research · 2026Article
- Novel trinucleotide mRNA capping reagents: improved synthetic route and efficient cotranscriptional incorporation in mRNA.RNA (New York, N.Y.) · 2026Article
- Synthesis, Incorporation, and Translation Properties of Threose Nucleic Acid Modified Trinucleotide Cap Analogs.ACS omega · 2025Article
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications.Experimental biology and medicine (Maywood, N.J.) · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
The recent COVID-19 pandemics have demonstrated the great therapeutic potential of in vitro transcribed (IVT) mRNAs, but improvements in their biochemical properties, such as cellular stability, reactogenicity and translational activity, are critical for further practical applications in gene replacement therapy and anticancer immunotherapy. One of the strategies to overcome these limitations is the chemical modification of a unique mRNA 5'-end structure, the 5'-cap, which is responsible for regulating translation at multiple levels. This could be achieved by priming the in vitro transcription reaction with synthetic cap analogs. In this study, we combined a highly efficient trinucleotide IVT capping technology with several modifications of the 5' cap triphosphate bridge to synthesize a series of 16 new cap analogs. We also combined these modifications with epigenetic marks (2'-O-methylation and m6Am) characteristic of mRNA 5'-ends in higher eukaryotes, which was not possible with dinucleotide caps. All analogs were compared for their effect on the interactions with eIF4E protein, IVT priming, susceptibility to decapping, and mRNA translation efficiency in model cell lines. The most promising α-phosphorothiolate modification was also evaluated in an in vivo mouse model. Unexpected differences between some of the analogs were analyzed using a protein cell extract pull-down assay.
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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.