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Updated: Sep 11, 2025
08:27
Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes
Published on: August 13, 2021
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Compact polyethylenimine-complexed mRNA vaccines
Jorge Moreno Herrero1, Theo B Stahl1, Stephanie Erbar1
1BioNTech SE, Mainz, Germany.
Nature Nanotechnology
|August 11, 2025
Summary
New self-amplifying RNA (saRNA) formulations complexed with polyethylenimine (PEI) show enhanced vaccine activity. These compact nanoparticles improve immune responses at lower doses, offering potential for broader prophylactic and therapeutic applications.
Area of Science:
- Biotechnology
- Molecular Biology
- Vaccine Development
Background:
- Self-amplifying RNA (saRNA) holds promise for vaccines and therapeutics.
- Previous saRNA formulations faced challenges with activity and delivery.
- Understanding saRNA complexation is key to improving efficacy.
Purpose of the Study:
- To develop novel polymer-complexed saRNA formulations with enhanced biological activity.
- To investigate the structural and functional properties of these new formulations.
- To assess their potential for vaccination and genetic material delivery.
Main Methods:
- Formulation of individual saRNA molecules with cationic polymer polyethylenimine (PEI).
- Characterization of nanoparticle size, structure, and stability.
- In vitro and in vivo evaluation of biological activity and immune responses in vaccination models.
Main Results:
- PEI-complexed saRNA formed compact nanoparticles (~30 nm) with high packing density.
- These formulations demonstrated enhanced biological activity compared to previous versions.
- Lower doses achieved relevant immune responses in vaccination models.
- A direct correlation was found between the single-molecule fraction and activity.
Conclusions:
- Novel PEI-complexed saRNA formulations offer improved efficacy for vaccines.
- The compact, single-molecule format is crucial for enhanced biological activity.
- These nanoparticles show potential for effective systemic delivery of genetic material.
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