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We applied emerging label-free biophysical techniques to map the size, composition and shape of RNA lipid nanoparticles. By linking these physical measurements to gene expression in human T cells and mice, we uncovered structure–activity relationships that guide RNA delivery.
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References
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Ma, Y., VanKeulen-Miller, R. & Fenton, O. S. mRNA lipid nanoparticle formulation, characterization and evaluation. Nat. Protoc. 20, 2618–2651 (2025). A protocol for how to formulate mRNA LNPs and characterize them using traditional analytical methods.
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Pardi, N. & Krammer, F. mRNA vaccines for infectious diseases — advances, challenges and opportunities. Nat. Rev. Drug Discov. 23, 838–861 (2024). A comprehensive review that details how mRNA LNPs were used for COVID-19 and are being designed for other infectious diseases.
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Parot, J. et al. Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques. J. Control. Release 367, 385–401 (2024). A holistic review and analysis of analytical methods to characterize LNPs.
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Li, S. et al. Payload distribution and capacity of mRNA lipid nanoparticles. Nat. Commun. 13, 5561 (2022). An example of a high-resolution technique developed to characterize LNPs, establish SARs and provide mechanistic insights into LNP formulation and delivery.
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Hopkins, J. B. BioXTAS RAW 2: new developments for a free open-source program for small-angle scattering data reduction and analysis. J. Appl. Cryst. 57, 194–208 (2024). This paper details BioXTAS RAW, the open-source program that can deconvolve, analyze and provide modeling for SEC–SAXS data.
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This is a summary of: Padilla, M. S. et al. Elucidating lipid nanoparticle properties and structure through biophysical analyses. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02855-x (2025).
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Solution biophysics reveals the polydisperse structure of RNA lipid nanoparticles.
Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02909-0
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DOI: https://doi.org/10.1038/s41587-025-02909-0
