Evidence map›Paper›PMID 37270636›Full record

ArticleScientific reports2023

Oligonucleotide mapping via mass spectrometry to enable comprehensive primary structure characterization of an mRNA vaccine against SARS-CoV-2.

Brian C Gau, Andrew W Dawdy, Hanliu Leah Wang, Bradley Bare, Carlos H Castaneda, Olga V Friese, Matthew S Thompson, Thomas F Lerch, David J Cirelli, Jason C Rouse

Abstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
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  3. Review
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  5. Integrating mass spectrometry with Nanopore direct RNA sequencing forbioRxiv : the preprint server for biology · 2026
    Article
  6. RNase 4 improves bottom-up modification mapping ofbioRxiv : the preprint server for biology · 2026
    Article
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  8. Article
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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

10 authors.

Brian C Gau *BioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA. Brian.Gau@pfizer.com.
Andrew W Dawdy *BioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA. Andrew.Dawdy@pfizer.com.
Hanliu Leah WangBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA.
Bradley BareBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA.
Carlos H CastanedaBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA.
Olga V FrieseBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA.
Matthew S ThompsonBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Andover, MA, USA.
Thomas F LerchBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Chesterfield, MO, USA.
David J CirelliBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Andover, MA, USA.
Jason C RouseBioTherapeutics Pharmaceutical Sciences, Pfizer Inc, Andover, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oligonucleotide mapping via liquid chromatography with UV detection coupled to tandem mass spectrometry (LC-UV-MS/MS) was recently developed to support development of Comirnaty, the world's first commercial mRNA vaccine which immunizes against the SARS-CoV-2 virus. Analogous to peptide mapping of therapeutic protein modalities, oligonucleotide mapping described here provides direct primary structure characterization of mRNA, through enzymatic digestion, accurate mass determinations, and optimized collisionally-induced fragmentation. Sample preparation for oligonucleotide mapping is a rapid, one-pot, one-enzyme digestion. The digest is analyzed via LC-MS/MS with an extended gradient and resulting data analysis employs semi-automated software. In a single method, oligonucleotide mapping readouts include a highly reproducible and completely annotated UV chromatogram with 100% maximum sequence coverage, and a microheterogeneity assessment of 5' terminus capping and 3' terminus poly(A)-tail length. Oligonucleotide mapping was pivotal to ensure the quality, safety, and efficacy of mRNA vaccines by providing: confirmation of construct identity and primary structure and assessment of product comparability following manufacturing process changes. More broadly, this technique may be used to directly interrogate the primary structure of RNA molecules in general.

Indexed as

COVID-19Tandem Mass SpectrometryChromatography, LiquidCOVID-19 VaccinesHumansmRNA VaccinesOligonucleotidesPeptide MappingRNA, MessengerSARS-CoV-2COVID-19 VaccinesmRNA VaccinesOligonucleotidesRNA, Messenger

Identifiers

PMID37270636
PMCPMC10239040

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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.