ArticleNature communications2025
Freezing induced incorporation of betaine in lipid nanoparticles enhances mRNA delivery.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Review
- Storage Buffer Composition Impacts Internal Structure, Freeze-Thaw Stability, and Transfection Efficiency of mRNA-Lipid Nanoparticles.ACS nano · 2026Article
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Innovative γ-Oryzanol and KC2 Based Lipid Nanoparticles: OryKL Platform Provides Safe and Efficient In Vivo mRNA Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Gauging lipid vulnerabilities in mRNA-LNPs under various environmental stressors through TIMS-TOF analysis.RSC advances · 2026Article
- Programmable lipid nanoparticles for RNA therapeutics: Design principles and clinical translation.Materials today. Bio · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) are key non-viral carriers for mRNA vaccines and therapeutics, but the inherent instability of mRNA necessitates sub-zero storage with cryoprotectants (CPAs) to prevent freeze-induced LNP aggregation and compromised mRNA delivery. Here we show that ice formation during freezing concentrates CPAs with LNPs in the remaining liquid-a phenomenon known as freeze concentration. This creates a steep concentration gradient of CPAs across the lipid membrane that drives passive CPAs diffusion into LNPs. By leveraging this process, we developed betaine-based CPAs that both preserve the stability of LNP and enter LNP during freeze-thaw. The incorporated betaine enhances endosomal escape and boosts mRNA delivery of LNP. In female mice, betaine-loaded LNPs elicit stronger humoral and cellular immune responses, providing dose-sparing advantages. These findings highlight freeze concentration as a promising LNP formulation strategy and underscore the role of CPA as active modulators of LNP structure and function.
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Registered trials
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