Lipid self-assembling nanoparticles as a novel platform for mRNA-based vaccination.
Publisher DOI
PubMed ID
41736889
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.
Date Issued
2026
Publication Type
Article
Subject(s)
Subjects
MT: Delivery Strategies
•
mRNA delivery
•
mRNA vaccine
•
self-assembling nanoparticles
•
protein corona
•
drug delivery
•
nanotechnology
Language(s)
en
Author(s)
De Chiara, Arianna | |
Nele, Valeria | |
Angelillo, Alessia | |
Campani, Virginia | |
Campanile, Andrea | |
Froechlich, Guendalina | |
Scognamiglio, Annagiulia | |
Pellino, Emilio | |
Greco, Antonietta | |
Chinello, Clizia | |
Pagani, Lisa | |
Corbo, Claudia | |
Nicosia, Alfredo | |
Sasso, Emanuele | |
De Rosa, Giuseppe |
Journal
Molecular Therapy: Nucleic Acids
Publisher
Cell Press
ISSN
2162-2531
Access(Rights)
open.access