Characterizing the Nanostructure of mRNA Vaccines by Small-angle Scattering

In modern mRNA-based vaccines, small lipid nanoparticles (LNPs) play an essential role since their structure has a strong impact on the vaccine’s biophysical properties. Here, we illustrate how small-angle scattering (SAS) can provide important structural information of these LNP-based vaccines and how to prove the presence of mRNA in the encapsulating carrier nanoparticles.


With the COVID pandemic, modern messenger RNA (mRNA)-based vaccines made a major breakthrough. This type of vaccines does not contain attenuated or dead viruses, but merely a “construction manual” for a component of the COVID-19 pathogen. For this purpose, a small piece of genetic information in the form of mRNA is encapsulated in a fat phase and transported into muscle cells. The phase used in these vaccine systems consists of lipid nanoparticles (LNPs) which are an essential component of the vaccine: the structure of the LNPs has an influence on the biophysical properties and the efficacy of the vaccine.1,2

Small-angle X-ray scattering (SAXS) is a method that measures the size and shape of nanosized particles and assemblies.3 SAXS is particularly suitable for studying biological and pharmacological samples because these materials are measured in solution, i.e. in their native state.

Today, modern laboratory SAXS systems allow the determination of particle diameters of up to approx. 300 nm. In addition, integrated sample changers can be used to run high-throughput measurements for screening multiple samples with, e.g. different formulations, buffers and concentrations.



1. Patel, S. et al. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nature Communications vol. 11 (2020).

2. Hassett, K. J. et al. Impact of lipid nanoparticle size on mRNA vaccine immunogenicity. Journal of Controlled Release vol. 335 237–246 (2021).

3. Schnablegger, H., Singh, Y., The SAXS Guide – Getting acquainted with the principles. 5th Ed. (2023), Anton Paar GmbH: Graz, Austria

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