ArticleMolecular therapy. Methods & clinical development2025
Characterization of intact mRNA-based therapeutics by charge detection mass spectrometry and mass photometry.
Article in Molecular therapy. Methods & clinical development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- From nucleotides to intact transcripts through oligonucleotides: Integrated chromatographic strategies for therapeutic mRNA characterization.Analytical and bioanalytical chemistry · 2026Review
- Advancing Charge Detection Mass Spectrometry for Characterizing Large, Intact mRNA Constructs.Analytical chemistry · 2026Article
- Modulating pressure in the Orbitrap improves sensitivity and mass resolution in charge detection mass spectrometry.Nature communications · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- Characterization of RNA using mass photometry: Method and technical perspectives.Molecular therapy. Nucleic acids · 2026Article
- Analyses of Individual Singly Charged Ions Using a High-Field Orbitrap Analyzer.Analytical chemistry · 2026Article
- End-to-end characterization of AAV manufacturing process using charge detection mass spectrometry.Molecular therapy. Methods & clinical development · 2025Article
- Drug Product Development of Lipid Nanoparticle-Based mRNA Therapeutics and Vaccines.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The impressive success of mRNA-based vaccines to combat COVID-19 has encouraged biopharmaceutical companies to invest in broader applications of alike vaccines for various diseases. Analytical approaches must keep pace to support this surge in the development of mRNA-based therapies. Intact mass analysis of mid- to large mRNA molecules (>1,000 nt) poses significant analytical challenges due to mRNA size, heterogeneity, and instability. Here, we demonstrate how single-particle Orbitrap-based charge detection mass spectrometry (CDMS) and mass photometry (MP) approaches can rapidly measure the mass of various intact high-mass capped mRNAs, up to 9,400 nt (∼3 MDa) in size. While ensemble MS yielded approximate masses for mRNAs <2,000 nt, it failed to provide information on samples of longer sequences. The drawbacks of ensemble MS could be avoided by recording individual ions. Low-charge mRNA components showed unstable ion behavior, hampering initial CDMS measurements, whereas high-charge populations offered better signal-to-noise and reduced charge uncertainty, with drastically improved mass accuracy. Lastly, in-solution MP enabled the measurement of mRNAs with high accuracy, while revealing low amounts of mRNA fragments and dimers that are sometimes overlooked in CDMS. Overall, CDMS and MP provide complementary methods that enable the study of large heterogeneous mRNA without requiring prior digestion or online separation.
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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.