Evidence map›Paper›PMID 40520363›Full record

ArticleMolecular therapy. Nucleic acids2025

Physicochemical and functional assessment of messenger RNA 5'Cap-end impurities under forced degradation conditions.

J Hutchinson, F Schweikart, R Shannon, A Murthy, S M Bates, S Leone, T Nissan, D Sideris, C Lal, J Button and 5 more

Abstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. High-throughput monitoring of free MgAnalytical and bioanalytical chemistry · 2026
    Article
  2. Article
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

15 authors.

J HutchinsonProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
F SchweikartAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
R ShannonProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
A MurthyProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
S M BatesImmune Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
S LeoneCell Therapy Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
T NissanImmune Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
D SiderisProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
C LalProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
J ButtonNucleic Acid Therapeutics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
R RaniNucleic Acid Therapeutics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
G ThomNucleic Acid Therapeutics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
N BondProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
E ÖrnskovAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
S TrabuloProcess and Analytical Sciences, BioPharmaceuticals Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The 5'Cap is a modified nucleotide structure added to the 5'end of mRNA, which plays a critical role in stability and translation of the molecule. Accurate characterization of 5'Cap impurities is crucial during development of mRNA therapeutics. Here, we utilized orthogonal liquid chromatography-mass spectrometry (LC-MS) workflows to characterize Cap-1-modified mRNA. A complex mixture of uncapped and, notably, 5'Cap chemical degradation variants, was detected. We subjected Cap-1 analogs to process-related forced degradation conditions and characterized multiple degradation routes of the 5'Cap structure, including hydrolysis and depurination. 5'Cap hydrolysis was observed in a representative

Indexed as

5′Capcritical quality attributesforced degradationliquid chromatography-mass spectrometryMT: oligonucleotides: therapies and applicationsRNA

Identifiers

PMID40520363
PMCPMC12166426

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.