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@ARTICLE{Sebastiani:892285,
author = {Sebastiani, Federica and Yanez Arteta, Marianna and Lerche,
Michael and Porcar, Lionel and Lang, Christian and Bragg,
Ryan A. and Elmore, Charles S. and Krishnamurthy, Venkata R.
and Russell, Robert A. and Darwish, Tamim and Pichler,
Harald and Waldie, Sarah and Moulin, Martine and Haertlein,
Michael and Forsyth, V. Trevor and Lindfors, Lennart and
Cárdenas, Marité},
title = {{A}polipoprotein {E} {B}inding {D}rives {S}tructural and
{C}ompositional {R}earrangement of m{RNA}-{C}ontaining
{L}ipid {N}anoparticles},
journal = {ACS nano},
volume = {15},
number = {4},
issn = {1936-086X},
address = {Washington, DC},
publisher = {Soc.},
reportid = {FZJ-2021-01995},
pages = {6709 - 6722},
year = {2021},
abstract = {Emerging therapeutic treatments based on the production of
proteins by delivering mRNA have become increasingly
important in recent times. While lipid nanoparticles (LNPs)
are approved vehicles for small interfering RNA delivery,
there are still challenges to use this formulation for mRNA
delivery. LNPs are typically a mixture of a cationic lipid,
distearoylphosphatidylcholine (DSPC), cholesterol, and a
PEG-lipid. The structural characterization of
mRNA-containing LNPs (mRNA-LNPs) is crucial for a full
understanding of the way in which they function, but this
information alone is not enough to predict their fate upon
entering the bloodstream. The biodistribution and cellular
uptake of LNPs are affected by their surface composition as
well as by the extracellular proteins present at the site of
LNP administration, e.g., apolipoproteinE (ApoE). ApoE,
being responsible for fat transport in the body, plays a key
role in the LNP’s plasma circulation time. In this work,
we use small-angle neutron scattering, together with
selective lipid, cholesterol, and solvent deuteration, to
elucidate the structure of the LNP and the distribution of
the lipid components in the absence and the presence of
ApoE. While DSPC and cholesterol are found to be enriched at
the surface of the LNPs in buffer, binding of ApoE induces a
redistribution of the lipids at the shell and the core,
which also impacts the LNP internal structure, causing
release of mRNA. The rearrangement of LNP components upon
ApoE incubation is discussed in terms of potential relevance
to LNP endosomal escape.},
cin = {JCNS-FRM-II / MLZ / JCNS-1 / JCNS-4},
ddc = {540},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 / I:(DE-588b)4597118-3 /
I:(DE-Juel1)JCNS-1-20110106 / I:(DE-Juel1)JCNS-4-20201012},
pnm = {6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ)
(POF4-6G4) / 632 - Materials – Quantum, Complex and
Functional Materials (POF4-632)},
pid = {G:(DE-HGF)POF4-6G4 / G:(DE-HGF)POF4-632},
experiment = {EXP:(DE-MLZ)KWS2-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {33754708},
UT = {WOS:000645436800066},
doi = {10.1021/acsnano.0c10064},
url = {https://juser.fz-juelich.de/record/892285},
}