On the interactions between RNA and titrateable lipid layers: implications for RNA delivery with lipid nanoparticles
Artikel i vetenskaplig tidskrift, 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.

Författare

Jennifer Gilbert

Lunds universitet

Inna Ermilova

Chalmers, Fysik, Nano- och biofysik

Marco Fornasier

Lunds universitet

Maximilian W.A. Skoda

STFC Rutherford Appleton Laboratory

Giovanna Fragneto

European Spallation Source (ESS)

Institut Laue-Langevin

Jan Swenson

Chalmers, Fysik, Nano- och biofysik

T. Nylander

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

Lunds universitet

Sungkyunkwan University

Nanoscale

2040-3364 (ISSN) 20403372 (eISSN)

Vol. 16 2 777-794

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Vetenskapsrådet (VR) (2017-06716), 2018-04-04 -- 2021-12-31.

Ämneskategorier

Fysikalisk kemi

Biokemi och molekylärbiologi

Den kondenserade materiens fysik

DOI

10.1039/d3nr03308b

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Senast uppdaterat

2024-03-07