Journal Article

PUBDB-2025-04819

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Compact polyethylenimine-complexed mRNA vaccines

Moreno Herrero, J. ; Stahl, T. B. ; Erbar, S. ; Maxeiner, K. ; Schlegel, A. ; Bacic, T. ; Schumacher, J. ; Cavalcanti, L. P. ; Schroer, M. A. ; Svergun, D. I. ; Sahin, U. (Corresponding author) ; Haas, H. (Corresponding author)

2025
Nature Publishing Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41565-025-01961-w

Abstract: Here we describe formulations comprising individual, polymer-complexed self-amplifying RNA (saRNA) molecules, designed for vaccination against infectious diseases and other prophylactic and therapeutic applications. When exposed to a large excess of the cationic polymer polyethylenimine (PEI), the single saRNA molecules in solution reorganize from an extended to a globular organization, characterized by a high packing density, low polymer mass fraction and, consequently, a very small size of the polyplex nanoparticles of about 30 nm. This format of PEI-complexed saRNA exhibits enhanced biological activity in comparison with previously described saRNA/PEI formulations, both in vitro and in vivo. In vaccination models, relevant immune responses at lower doses are achieved, offering potential advantages for practical use. We found that the single PEI-complexed RNA molecules are also present in conventional formulations to some degree. The direct correlation between the single-molecule fraction with activity suggests that it is this format that predominantly contributes to activity in the different formulation types. Complexation is driven by mechanisms of self-assembly between oppositely charged polyelectrolytes, making this protocol broadly applicable to various cationic polymers and RNA constructs. With their small size and good stability in biofluids, these compacted RNA molecules are also promising for the systemic delivery of genetic material to compartments that are difficult to reach with larger particles.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. EMBL (EMBL)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. SINE2020 - World class Science and Innovation with Neutrons in Europe 2020 – SINE2020 (654000) (654000)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Engineering, Computing and Technology ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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