Characterizing mRNA encapsulated in lipid nanoparticles (LNPs) is crucial but notoriously tricky. A recent study, “Proof of Concept Application of Hydrophilic Interaction Chromatography for Direct Online Disruption of Lipid Nanoparticles, Intact mRNA Analysis, and Measure of Encapsulation Efficiency,” by Davy Guillarme and his team at the University of Geneva, Switzerland, proposes a novel proof of concept method for online LNP disruption using Hydrophilic Interaction Chromatography (HILIC), eliminating the need for manual sample preparation.

Key Findings:
• HILIC enabled direct online disruption of LNPs, releasing and retaining intact mRNA for integrity analysis
• A second, milder HILIC method preserved LNPs and quantified free mRNA, enabling rapid encapsulation efficiency calculations
• The method accurately assessed a complex Sanofi mRNA product, yielding integrity and encapsulation data comparable to orthogonal techniques like RiboGreen and ion-exchange chromatography

Why It Matters: With further optimization, HILIC could become a vital tool for QC and formulation development in mRNA therapeutics. This approach drastically reduces hands-on time and risk of mRNA degradation while offering an orthogonal, high-throughput alternative to current analytical techniques. 

Read more: https://pubs.acs.org/doi/10.1021/acs.analchem.5c00565