Encapsulation of mRNA in Therapeutics Like Lipid Nanoparticles Probed by Deep-UV Resonance Raman Spectroscopy
Sila Jin, Sergei V. Reverdatto, Vladimir V. Ermolenkov, Alexander Shekhtman, Young Mee Jung, Igor K. Lednev
TL;DR
This study uses deep-UV resonance Raman spectroscopy to analyze how mRNA is encapsulated in lipid nanoparticles for therapeutic delivery.
Contribution
The first use of 2T2D-COS for quantitative analysis of lipid–mRNA interactions in mRNA therapeutics.
Findings
DUVRR spectroscopy can distinguish between fully encapsulated, partially exposed, and free mRNA.
PCA identified spectral variations between 1270 and 1800 cm–1 linked to lipid presence.
The 1322 cm–1 band was identified as a quantitative indicator of lipid–mRNA interactions.
Abstract
Messenger RNA (mRNA) therapeutics have emerged as a powerful platform for treating a wide range of diseases, but their clinical success depends on overcoming the issues of instability and delivery. mRNAs are typically unstable and require encapsulation in lipid nanoparticles (LNPs) for efficient delivery. This study quantifies free and encapsulated mRNAs within LNPs in a model vaccine using deep-UV resonance Raman (DUVRR) spectroscopy. DUVRR spectroscopy with excitation at 266 nm, matching the maximum UV absorption of mRNA, enables spectral differentiation of mRNA based on its degree of encapsulationfrom fully encapsulated to partially exposed to completely free. Raman spectra were acquired from the samples with progressively decreasing lipid concentrations while maintaining a fixed mRNA concentration; vibrational modes associated with mRNA–lipid interactions were identified. Principal…
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Taxonomy
TopicsSpectroscopy Techniques in Biomedical and Chemical Research · RNA Interference and Gene Delivery · Lipid Membrane Structure and Behavior