Journal of pharmaceutical sciencesNov 15, 2025

Stable mRNA vaccines without fats made using atomic layer deposition

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Atomic layer deposition produced lipid-free mRNA vaccine microparticles that stayed stable at warm temperatures and triggered immune responses in preclinical testing.

Evidence

Formulation and preclinical platform experiments used spray-dried polysaccharide microparticles with alumina shells carrying mRNAs for ovalbumin, N332-GT2, and GFP, with in vitro macrophage uptake, in vivo immune responses, and 6-month storage stability up to 40 °C.

Caveat

The evidence is preclinical and platform-based, with model antigens and animal or cell-system endpoints rather than human vaccine efficacy.

Simplified

Lipid nanoparticle (LNP) formulations of mRNA vaccines have played a pivotal role in combatting SARS-CoV-2 infections and are expected to be a useful vaccine modality against other pathogens. However, the instability of mRNA-LNP vaccines requires their storage at temperatures below 0 °C and presents manufacturing challenges. We describe thermally stable, lipid-free mRNA vaccines prepared by spray-drying to embed mRNA within glassy polysaccharide microparticles, followed by atomic layer deposition (ALD) to encapsulate the microparticles within protective alumina shells that provide temporally controlled antigen release and facilitate cellular uptake. Using mRNAs encoding for ovalbumin, the modified HIV envelope trimer protein N332-GT2, and green fluorescent protein (GFP), we show that alumina-coated microparticles containing lipid-free mRNA are internalized by cultured macrophages in vitro, elicit robust immune responses compared to LNP-based mRNA vaccines in vivo, and are stable when stored for 6 months at temperatures up to 40 °C. Thus, alumina-coated mRNA vaccines may overcome current limitations of mRNA-LNP vaccines without using LNPs or other lipid-based carriers.