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<p>Development of mRNA technologies has opened new horizons for both preventive vaccines and therapeutics. The rapid growth of mRNA products goes hand in hand with the need for novel analytical methods to characterize these products. One common critical quality attribute of mRNA Drug Substance (DS) and Drug Product (DP) is mRNA integrity. mRNA molecules are susceptible to degradation, often necessitating ultra-low-temperature storage of mRNA vaccines. Once degraded, mRNA can no longer be correctly translated into the target protein, leading to reduced vaccine efficacy. Therefore, robust analytical methods are crucial for understanding mRNA degradation mechanisms, optimizing formulation stability, and maximizing efficacy. In this study, we compared three analytical methods to assess mRNA integrity and purity: capillary gel electrophoresis (CGE) with fluorescent detection using a fragment analyzer (FA) device, CGE with ultraviolet (UV) detection, and ion-pairing reversed-phase chromatography (IP-RPLC) with UV detection. All three methods successfully monitored the integrity of mRNA DS and DP. IP-RPLC provided better resolution and facilitated the detection of mRNA-lipid adducts, while the FA, being more automated, enabled rapid analysis of a large number of samples. CGE-UV revealed the presence of mRNA oligomers. Further analysis showed that these oligomers could express the target protein similarly to the mRNA monomer.</p>

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Comparative study of analytical methods for assessing mRNA integrity and identification of functional mRNA oligomers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Perrine Lardellier,
  • Camille Malburet,
  • Marco Morani,
  • Thibaut Willemin,
  • Javier Rol-Moreno,
  • Anouck Noir,
  • Stéphanie Fertier-Prizzon,
  • Marc Francois-Heude

摘要

Development of mRNA technologies has opened new horizons for both preventive vaccines and therapeutics. The rapid growth of mRNA products goes hand in hand with the need for novel analytical methods to characterize these products. One common critical quality attribute of mRNA Drug Substance (DS) and Drug Product (DP) is mRNA integrity. mRNA molecules are susceptible to degradation, often necessitating ultra-low-temperature storage of mRNA vaccines. Once degraded, mRNA can no longer be correctly translated into the target protein, leading to reduced vaccine efficacy. Therefore, robust analytical methods are crucial for understanding mRNA degradation mechanisms, optimizing formulation stability, and maximizing efficacy. In this study, we compared three analytical methods to assess mRNA integrity and purity: capillary gel electrophoresis (CGE) with fluorescent detection using a fragment analyzer (FA) device, CGE with ultraviolet (UV) detection, and ion-pairing reversed-phase chromatography (IP-RPLC) with UV detection. All three methods successfully monitored the integrity of mRNA DS and DP. IP-RPLC provided better resolution and facilitated the detection of mRNA-lipid adducts, while the FA, being more automated, enabled rapid analysis of a large number of samples. CGE-UV revealed the presence of mRNA oligomers. Further analysis showed that these oligomers could express the target protein similarly to the mRNA monomer.