Apolipoprotein E binding drives structural and compositional rearrangement of mRNA-containing lipid nanoparticles
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., 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.
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Other researchers propose that the outer shell of mRNA-LNPs consists of one or multiple bilayers.
“Other researchers propose that the outer shell of mRNA-LNPs consists of one or multiple bilayers, based on cryo-TEM analysis (Fig. 2) (Patel et al., 2020, Tanaka et al., 2020) or SANS (Sebastiani et al., 2021).”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Sebastiani et al., 2021
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- Authors
- Sebastiani, F., Yanez Arteta, M., Lerche, M., Porcar, L., Lang, C., Bragg, R. A., Elmore, C. S., Krishnamurthy, V. R., Russell, R. A., Darwish, T., Pichler, H., Waldie, S., Moulin, M., Haertlein, M., Forsyth, V. T., Lindfors, L., & Cárdenas, M.
- Affiliations
- Malmö University (SE)
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 431 83 Gothenburg Sweden
- AstraZeneca (Sweden) (SE)
- Institut Laue-Langevin (FR)
- Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science JCNS, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstraße 1, 85748 Garching, Germany
- AstraZeneca (United Kingdom) (GB)
- AstraZeneca (United States) (US)
- Australian Nuclear Science and Technology Organisation (AU)
- Graz University of Technology (AT)
- Corresponding author
- Sebastiani, Federica
- Cárdenas, Marité
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-03-23
- Volume
- 15
- Issue
- 4
- Pages
- 6709-6722
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC8155318
- OpenAlex
- W3137338783
- Cited by
- 409
- References
- 65
- Citations by year
- 2026: 92 · 2025: 101 · 2024: 99 · 2023: 58 · 2022: 45 · 2021: 13
- FWCI
- 16.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- ACS Nano (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion, cc-by)
- Keele Research Repository (Keele University) (submittedVersion, cc-by)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- iMPULSE (Heinz Maier-Leibnitz Zentrum) (submittedVersion, other-oa)
- Funders
- Engineering and Physical Sciences Research Council (EP/C015452/1, GR/R99393/01)
- Vetenskapsr?det (2014-3981, 2018-03990, 2018-0483)
- Stiftelsen f?r Kunskaps- och Kompetensutveckling (20180101)
- Horizon 2020 Framework Programme (654000, 731019)
- National Science Foundation USA (DMR-0520547)
- National Collaborative Research Infrastructure Strategy (NCRIS)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- apolipoprotein E, lipid nanoparticles, mRNA delivery, lipid binding, lipid redistribution, cholesterol, DSPC, nanoparticle structure, mRNA release, endosomal escape, selective deuteration
- MeSH terms
- Apolipoproteins E, RNA, Messenger, Tissue Distribution, RNA, Small Interfering, Nanoparticles
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