Elucidating the underlying mechanism of mechanical stress-induced impact on mRNA-LNP structure

Oct 31, 2025Scientific reports

How mechanical stress may change the structure of mRNA lipid nanoparticles

AI simplified

mRNA Technology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A significant increase in particle sizes and heterogeneity of mRNA-lipid nanoparticles was observed after 240 minutes of shaking.

Minimal impact on mRNA-lipid nanoparticles occurs after 30 minutes of shaking.
Cryogenic electron microscopy revealed larger mRNA-lipid nanoparticle structures after prolonged shaking.
Decreased particle concentrations were noted alongside increased sizes and heterogeneity after 240 minutes.
Unencapsulated RNA was detected following extended shaking of mRNA-lipid nanoparticles.
Changes in lipid mobility at the mRNA-lipid nanoparticle surface were indicated by nuclear magnetic resonance analysis.

AI simplified

The COVID-19 pandemic has demonstrated the suitability of mRNA-lipid nanoparticle (LNP) drug product as an appropriate vaccine for emergency response during a global health crisis. Understanding of mRNA-LNPs stability and mechanisms of degradation is important; however a deeper mechanistic understanding of the impact of liquid-air interfaces on is still absent. This study used a combination of nanoparticle tracking analysis (), nuclear magnetic resonance () spectroscopy and cryogenic electron microscopy (cryo-EM) to elucidate the dynamics occurring during shaking induced stress on mRNA-LNPs. Minimal impact is observed for mRNA-LNPs upon 30 min of shaking. However, a significant increase of particle sizes and heterogeneity, accompanied by a decrease of particle concentrations were observed by NTA upon 240 min of shaking. Cryo-EM imaging showed the formation of larger mRNA-LNP structures, which was consistent with the NTA results. Additionally, unencapsulated RNA was observed with RNA staining after prolonged shaking of mRNA-LNPs. NMR suggests that the mRNA-LNP surface structure changes significantly which was marked by changes in the lipid mobility of the PEGylated and ionizable lipids. NMR also detected distinct sucrose signals owing to the movement from the bulk solution into the larger mRNA-LNPs. Collectively, the suite of these techniques provides a deeper understanding of the dynamics leading to morphological changes of mRNA-LNPs under mechanical stress conditions by shaking.

Key numbers

84.6 nm

Increase in Particle Size

Mean diameter after 240 min of shaking

6.81×10¹² particles/mL

Decrease in Particle Concentration

Particle concentration after 240 min of shaking

52.0 nm

Initial Particle Size

Mean diameter after 30 min of shaking

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗View full text (HTML) ↗

Elucidating the underlying mechanism of mechanical stress-induced impact on mRNA-LNP structure

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief

Abstract

Key numbers

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief