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Apolipoprotein E Bi...
Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles
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- Sebastiani, Federica (author)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Yanez Arteta, Marianna (author)
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
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- Lerche, Michael (author)
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
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- Porcar, Lionel (author)
- Large Scale Structures, Institut Laue Langevin, Grenoble F-38042, France
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- Lang, Christian (author)
- Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science JCNS, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstraße 1, 85748 Garching, Germany
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- Bragg, Ryan A. (author)
- Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, SK 10 4TG Cambridge, U.K.
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- Elmore, Charles S. (author)
- Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg, Sweden
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- Krishnamurthy, Venkata R. (author)
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, CB2 0AA Boston, Massachusetts 02451, United States
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- Russell, Robert A. (author)
- National Deuteration Facility (NDF), Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, 2232 Sydney, NSW, Australia
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- Darwish, Tamim (author)
- National Deuteration Facility (NDF), Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, 2232 Sydney, NSW, Australia
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- Pichler, Harald (author)
- 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
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- Waldie, Sarah (author)
- 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
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- Moulin, Martine (author)
- Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France
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- Haertlein, Michael (author)
- Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France;Partnership for Structural Biology (PSB), Grenoble F-38042, France
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- Forsyth, V. Trevor (author)
- 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.
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- Lindfors, Lennart (author)
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
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- Cárdenas, Marité (author)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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(creator_code:org_t)
- 2021-03-23
- 2021
- English.
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:4, s. 6709-6722
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https://mau.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Keyword
- ApoE
- lipid nanoparticles
- mRNA delivery
- protein corona
- small-angle scattering
Publication and Content Type
- ref (subject category)
- art (subject category)
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ACS Nano
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- By the author/editor
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Sebastiani, Fede ...
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Yanez Arteta, Ma ...
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Lerche, Michael
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Porcar, Lionel
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Lang, Christian
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Bragg, Ryan A.
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show more...
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Elmore, Charles ...
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Krishnamurthy, V ...
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Russell, Robert ...
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Darwish, Tamim
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Pichler, Harald
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Waldie, Sarah
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Moulin, Martine
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Haertlein, Micha ...
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Forsyth, V. Trev ...
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Lindfors, Lennar ...
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Cárdenas, Marité
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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and Physical Chemist ...
- Articles in the publication
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ACS Nano
- By the university
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Malmö University