Encapsulation state of messenger RNA inside lipid nanoparticles

Understanding the structure of messenger RNA (mRNA) lipid nanoparticles, and specifically the microenvironment of the mRNA molecules within these entities, is fundamental to advancing their biomedical potential. Here, we show that a permeating cationic dye, thionine, can serve as a cryogenic electron microscopy contrasting agent by binding selectively to encapsulated mRNA without disturbing lipid nanoparticle morphology. Cryo-electron microscopy images identify the mRNA location, revealing that mRNA may exist within solvent-filled cavities or may be substantially lipid associated.

Automated summary

Understanding the structure and microenvironment of mRNA within lipid nanoparticles is crucial for unlocking their biomedical potential. By using the permeating cationic dye thionine as a contrasting agent, cryo-electron microscopy images reveal the location of mRNA within the nanoparticles, suggesting it may be in solvent-filled cavities or associated with lipids.