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Sökning: id:"swepub:oai:DiVA.org:mau-62966" > Apolipoprotein E Bi...

Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles

Sebastiani, Federica (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
Yanez Arteta, Marianna (författare)
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
Lerche, Michael (författare)
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
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Porcar, Lionel (författare)
Large Scale Structures, Institut Laue Langevin, Grenoble F-38042, France
Lang, Christian (författare)
Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science JCNS, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstraße 1, 85748 Garching, Germany
Bragg, Ryan A. (författare)
Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, SK 10 4TG Cambridge, U.K.
Elmore, Charles S. (författare)
Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg, Sweden
Krishnamurthy, Venkata R. (författare)
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, CB2 0AA Boston, Massachusetts 02451, United States
Russell, Robert A. (författare)
National Deuteration Facility (NDF), Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, 2232 Sydney, NSW, Australia
Darwish, Tamim (författare)
National Deuteration Facility (NDF), Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, 2232 Sydney, NSW, Australia
Pichler, Harald (författare)
Austrian Centre of Industrial Biotechnology, Petersgasse 14, 8010, Graz, Austria;Institute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, BioTechMed Graz, Petersgasse 14, 8010, Graz, Austria
Waldie, Sarah (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France
Moulin, Martine (författare)
Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France
Haertlein, Michael (författare)
Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France
Forsyth, V. Trevor (författare)
Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France;Faculty of Natural Sciences, Keele University, Staffordshire, ST5 5BG, U.K.
Lindfors, Lennart (författare)
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
Cárdenas, Marité (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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 (creator_code:org_t)
2021-03-23
2021
Engelska.
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:4, s. 6709-6722
Relaterad länk:
https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
https://pubs.acs.org...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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. 

Ämnesord

NATURVETENSKAP  -- Kemi -- Fysikalisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Physical Chemistry (hsv//eng)

Nyckelord

ApoE
lipid nanoparticles
mRNA delivery
protein corona
small-angle scattering

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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  • ACS Nano (Sök värdpublikationen i LIBRIS)

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