ArticleAnalytical chemistry2024
Comprehensive Impurity Profiling of mRNA: Evaluating Current Technologies and Advanced Analytical Techniques.
Article in Analytical chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026Article
- mRNA-based therapeutics in lung Cancer: Mechanisms, applications, and translational challenges.Journal, genetic engineering & biotechnology · 2026Review
- Advancing Charge Detection Mass Spectrometry for Characterizing Large, Intact mRNA Constructs.Analytical chemistry · 2026Article
- Review
- 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
- Transcript-independent quantitative analysis of RNA cap structures by LC-MS/MS.Molecular therapy. Advances · 2026Article
- A circular RNA vaccine induces durable and cross-protective immunity against Neisseria meningitidis serogroup B in mice.PLoS pathogens · 2026Article
- Autoimmune Features of Post-COVID-19 Vaccination Syndrome and Their Impacts on the Renin-Angiotensin System.Vaccines · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Process and analytical strategies for the safe production of mRNA vaccines and therapeutics.Molecular biology reports · 2026Review
- Regulatory framework for polymer-based nanotherapeutics in clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Challenges and advances in analytical separation techniques for RNA-lipid nanoparticle therapeutics.Analytical and bioanalytical chemistry · 2026Review
- Comparative study of analytical methods for assessing mRNA integrity and identification of functional mRNA oligomers.Scientific reports · 2025Article
- The impact of chemical reactivity on the quality and stability of RNA-LNP pharmaceuticals.Nature reviews. Chemistry · 2025Review
- Size-exclusion chromatography with post-column nucleic acid staining and fluorescence detection for sensitive ribonucleic acid analysis.Analytical and bioanalytical chemistry · 2025Article
- Characterization of intact mRNA-based therapeutics by charge detection mass spectrometry and mass photometry.Molecular therapy. Methods & clinical development · 2025Article
- Removal of dsRNA byproducts using affinity chromatography.Molecular therapy. Nucleic acids · 2025Article
- Comparative Analysis of mRNA Degradation Kinetics Using Chromatographic and Electrophoretic Methods.Molecular pharmaceutics · 2025Article
- Current Analytical Strategies for mRNA-Based Therapeutics.Molecules (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro transcription (IVT) of mRNA is a versatile platform for a broad range of biotechnological applications. Its rapid, scalable, and cost-effective production makes it a compelling choice for the development of mRNA-based cancer therapies and vaccines against infectious diseases. The impurities generated during mRNA production can potentially impact the safety and efficacy of mRNA therapeutics, but their structural complexity has not been investigated in detail yet. This study pioneers a comprehensive profiling of IVT mRNA impurities, integrating current technologies with innovative analytical tools. We have developed highly reproducible, efficient, and stability-indicating ion-pair reversed-phase liquid chromatography and capillary gel electrophoresis methods to determine the purity of mRNA from different suppliers. Furthermore, we introduced the applicability of microcapillary electrophoresis for high-throughput (<1.5 min analysis time per sample) mRNA impurity profiling. Our findings revealed that impurities are mainly attributed to mRNA variants with different poly(A) tail lengths due to aborted additions or partial hydrolysis and the presence of double-stranded mRNA (dsRNA) byproducts, particularly the dsRNA 3'-loop back form. We also implemented mass photometry and native mass spectrometry for the characterization of mRNA and its related product impurities. Mass photometry enabled the determination of the number of nucleotides of different mRNAs with high accuracy as well as the detection of their size variants [i.e., aggregates and partial and/or total absence of the poly(A) tail], thus providing valuable information on mRNA identity and integrity. In addition, native mass spectrometry provided insights into mRNA intact mass, heterogeneity, and important sequence features such as poly(A) tail length and distribution. This study highlights the existing bottlenecks and opportunities for improvement in the analytical characterization of IVT mRNA, thus contributing to the refinement and streamlining of mRNA production, paving the way for continued advancements in biotechnological applications.
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Registered trials
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