ArticleNature communications2021
A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
What it found
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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.
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.
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Who cites it
123 citing papers in PubMed.
- Accelerated discovery of thermostable mRNA-lipid nanoparticle vaccines using data-efficient AI.Nature biotechnology · 2026Article
- Preparation of Targeted Delivery Materials and Their Application in Animal Production.Animals : an open access journal from MDPI · 2026Review
- Ligand-Mediated Reprogramming Redirects Liver-Tropic Ionizable Lipid Nanoparticles for Lung-Selective mRNA Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Comprehensive Analytical Characterization of mRNA Influenza Vaccine Under Stress Conditions: Implications for Stability and Quality Control.Pharmaceutical research · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Critical Evaluation of Key Methods for RNA Quantification.International journal of molecular sciences · 2026Review
- Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation.Discover nano · 2026Review
- Composite biomaterials of polyelectrolyte complex micelle nanoparticles in hyaluronic acid gels enable local, targeted miR-92a inhibition and enhanced angiogenesis in diabetic wound repair.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Amine oxide lipid nanoparticles for delivery of cyclic dinucleotides.National science review · 2026Article
- Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026Article
- Review
- Peptide additives reprogram the lipid nanoparticle corona and enhance gene delivery in a serum-free environment for lung epithelium.bioRxiv : the preprint server for biology · 2026Article
- Advances in delivery technologies-powered cancer vaccines.Bioactive materials · 2026Review
- Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.ACS nano · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- Antioxidant lipid nanoparticles enhance mRNA stability for regeneration therapy and gene editing.Nature communications · 2026Article
- Review
- Impact of ionizable lipid source on quality and stability of siRNA-loaded lipid nanoparticles.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- Emerging Non-Conventional Approaches in mRNA-LNP Formulation for Therapeutic Applications.Pharmaceutics · 2026Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticle (LNP)-formulated mRNA vaccines were rapidly developed and deployed in response to the SARS-CoV-2 pandemic. Due to the labile nature of mRNA, identifying impurities that could affect product stability and efficacy is crucial to the long-term use of nucleic-acid based medicines. Herein, reversed-phase ion pair high performance liquid chromatography (RP-IP HPLC) was used to identify a class of impurity formed through lipid:mRNA reactions; such reactions are typically undetectable by traditional mRNA purity analytical techniques. The identified modifications render the mRNA untranslatable, leading to loss of protein expression. Specifically, electrophilic impurities derived from the ionizable cationic lipid component are shown to be responsible. Mechanisms implicated in the formation of reactive species include oxidation and subsequent hydrolysis of the tertiary amine. It thus remains critical to ensure robust analytical methods and stringent manufacturing control to ensure mRNA stability and high activity in LNP delivery systems.
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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.