Evidence map›Paper›PMID 42699029›Full record

ArticleMolecular therapy. Nucleic acids2026

Sub-stoichiometric 5-methoxyuridine modification enables tunable immune evasion and protein expression from synthetic mRNAs.

Jonathan R Miles, Sarah Masterson, Eleanor Bellows, Fabio Fisher, Ritu Rani, Sara Marelli, Colin Hardman, Luigi Grassi, Luis Santos, Victoria James and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Jonathan R MilesSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Sarah MastersonSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Eleanor BellowsSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Fabio FisherBiopharmaceuticals R&D, Discovery Sciences, Nucleic Acid Therapeutics, RNA Therapy Team, AstraZeneca, CB2 0AA Cambridge, UK.
Ritu RaniBiopharmaceuticals R&D, Discovery Sciences, Nucleic Acid Therapeutics, RNA Therapy Team, AstraZeneca, CB2 0AA Cambridge, UK.
Sara MarelliBiopharmaceuticals R&D, Discovery Sciences, Nucleic Acid Therapeutics, RNA Therapy Team, AstraZeneca, CB2 0AA Cambridge, UK.
Colin HardmanBiopharmaceuticals R&D, Data Science & Advanced Analytics, Data Science and AI, AstraZeneca, CB2 0AA Cambridge, UK.
Luigi GrassiBiopharmaceuticals R&D, Biopharmaceutical Development, AstraZeneca, CB2 0AA Cambridge, UK.
Luis SantosBiopharmaceuticals R&D, Biopharmaceutical Development, AstraZeneca, Gaithersburg, MD 20878, USA.
Victoria JamesSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Nigel P MonganSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Christopher J HayesSchool of Chemistry, University of Nottingham, NG7 2RD Nottingham, UK.
Matthew LooseSchool of Life Sciences, University of Nottingham, NG7 2RD Nottingham, UK.
Janet M DalySchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
James ButtonBiopharmaceuticals R&D, Discovery Sciences, Nucleic Acid Therapeutics, RNA Therapy Team, AstraZeneca, CB2 0AA Cambridge, UK.
George ThomBiopharmaceuticals R&D, Discovery Sciences, Nucleic Acid Therapeutics, RNA Therapy Team, AstraZeneca, CB2 0AA Cambridge, UK.
Rupert G FraySchool of Biosciences, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.
Nathan ArcherSchool of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, LE12 5RD Leicestershire, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

mRNA therapeutics depend on nucleotide modification to evade innate immunity and sustain translation. Current clinical designs replace all uridine with N1-methylpseudouridine (m1Ψ). However, full substitution is costly and can perturb translational fidelity and RNA structure. Here, we show that sub-stoichiometric incorporation of 5-methoxyuridine (5moU) is sufficient to confer immune evasion while enhancing protein output. Substitution of 25% of uridines with 5moU supported translation comparable to fully m1Ψ-modified mRNA in some cell types, while 50% 5moU maximized expression across all systems tested, often outperforming 100% m1Ψ-modified mRNA. This effect was conserved in human primary cells and

Indexed as

5-methoxy-uracilepitranscriptomemRNA therapeuticsMT: oligonucleotides: therapies and applications

Identifiers

PMID42699029
PMCPMC13543807

What OpenQuestion holds

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Registered trials

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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.