On the interactions between RNA and titrateable lipid layers: implications for RNA delivery with lipid nanoparticles
Journal article, 2023

Characterising the interaction between cationic ionisable lipids (CIL) and nucleic acids (NAs) is key to understanding the process of RNA lipid nanoparticle (LNP) formation and release of NAs from LNPs. Here, we have used different surface techniques to reveal the effect of pH and NA type on the interaction with a model system of DOPC and the CIL DLin-MC3-DMA (MC3). At only 5% MC3, differences in the structure and dynamics of the lipid layer were observed. Both pH and %MC3 were shown to affect the absorption behaviour of erythropoietin mRNA, polyadenylic acid (polyA) and polyuridylic acid (polyU). The adsorbed amount of all studied NAs was found to increase with decreasing pH and increasing %MC3 but with different effects on the lipid layer, which could be linked to the NA secondary structure. For polyA at pH 6, adsorption to the surface of the layer was observed, whereas for other conditions and NAs, penetration of the NA into the layer resulted in the formation of a multilayer structure. By comparison to simulations excluding the secondary structure, differences in adsorption behaviours between polyA and polyU could be observed, indicating that the NA's secondary structure also affected the MC3-NA interactions.

Author

Jennifer Gilbert

Lund University

Inna Ermilova

Chalmers, Physics, Nano and Biophysics

Marco Fornasier

Lund University

Maximilian W.A. Skoda

STFC Rutherford Appleton Laboratory

Giovanna Fragneto

European Spallation Source (ESS)

Institut Laue-Langevin

Jan Swenson

Chalmers, Physics, Nano and Biophysics

T. Nylander

Lund Institute of Advanced Neutron and X-ray Science (LINXS)

Lund University

Sungkyunkwan University

Nanoscale

2040-3364 (ISSN) 20403372 (eISSN)

Vol. 16 2 777-794

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Subject Categories

Physical Chemistry

Biochemistry and Molecular Biology

Condensed Matter Physics

DOI

10.1039/d3nr03308b

More information

Latest update

3/7/2024 9