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On the interactions between RNA and titrateable lipid layers : implications for RNA delivery with lipid nanoparticles

Gilbert, Jennifer LU orcid ; Ermilova, Inna ; Fornasier, Marco LU orcid ; Skoda, Maximilian ; Fragneto, Giovanna ; Swenson, Jan and Nylander, Tommy LU (2023) In Nanoscale
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Nanoscale
publisher
Royal Society of Chemistry
external identifiers
  • pmid:38088740
  • scopus:85180104905
ISSN
2040-3364
DOI
10.1039/d3nr03308b
language
English
LU publication?
yes
id
c43d4b40-9823-4895-84f8-a9392ddd72ae
date added to LUP
2024-01-10 09:38:39
date last changed
2024-04-25 05:37:31
@article{c43d4b40-9823-4895-84f8-a9392ddd72ae,
  abstract     = {{<p>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.</p>}},
  author       = {{Gilbert, Jennifer and Ermilova, Inna and Fornasier, Marco and Skoda, Maximilian and Fragneto, Giovanna and Swenson, Jan and Nylander, Tommy}},
  issn         = {{2040-3364}},
  language     = {{eng}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Nanoscale}},
  title        = {{On the interactions between RNA and titrateable lipid layers : implications for RNA delivery with lipid nanoparticles}},
  url          = {{http://dx.doi.org/10.1039/d3nr03308b}},
  doi          = {{10.1039/d3nr03308b}},
  year         = {{2023}},
}