Lipid self-assembling nanoparticles as a novel platform for mRNA-based vaccination.
Year: 2026
Type: article
Abstract: Synthetic messenger RNA (mRNA) formulated in lipid nanoparticles (mRNA-LNPs) is a promising candidate for next-generation gene therapy and genetic vaccines. However, mRNA-LNP formulations require low-temperature storage to ensure proper transport and distribution. Here, we introduce a lipid self-assembling nanoparticle (SANP) technology to address the stability challenges of mRNA-based therapeutics. SANP formulations can be prepared by simply mixing the components immediately before use, allowing mRNA vaccines to be stored and transported at 4°C without freezing, thereby enhancing their stability. SANPs loaded with mRNA (mRNA-SANPs) exhibited a sub-200 nm size, high mRNA encapsulation efficiency, colloidal stability post-assembly and in human plasma, and low hemolytic activity. Intramuscular (IM) and intravenous (IV) administration of mRNA-SANPs encoding a reporter gene in mice resulted in high levels of transgene expression, with no observed renal or hepatic toxicity and no release of pro-inflammatory cytokines. Additionally, protein fingerprint analysis of mRNA-SANPs in serum identified specific nanoparticle-protein interactions that correlated with in vivo biodistribution. Finally, mRNA-SANPs encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein elicited a significant immune response in mice following both IM and IV administration.[Figure: see text]De Rosa and colleagues demonstrate that self-assembling nanoparticles encapsulating mRNA induce the expression of mRNA-encoded proteins and an immune response in vivo. The on-demand preparation of the formulations enables storage of the mRNA vaccine at 4°C and overcomes some of the stability challenges faced by current mRNA-based formulations.
DOI: 10.48620/96057
Authors: De Chiara, Arianna, Nele, Valeria, Angelillo, Alessia, Campani, Virginia, Campanile, Andrea, Froechlich, Guendalina, Scognamiglio, Annagiulia, Pellino, Emilio, Greco, Antonietta, Chinello, Clizia, Pagani, Lisa, Eugster, Remo, Luciani, Paola, Corbo, Claudia, Nicosia, Alfredo, Sasso, Emanuele, De Rosa, Giuseppe
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7134913675