DOI > 10.5291/ILL-DATA.8-02-1035

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Title

Unravelling LNP endosome escape

Abstract

In this proposal we aim to deepen our understanding of the endosomal escape mechanism, a crucial aspect for enhancing the therapeutic efficacy of lipid nanoparticles (LNPs) in drug delivery, exemplified by the success of formulations like the Comirnaty and mRNA-1273 Covid-19 vaccines. An optical microscopy-based assay developed by the Fredrik Höök group, allow us to observe individual LNP binding events to a supported lipid bilayer (ncSLB) mimicking the endosomal membrane. Neutron reflection experiment conducted at ISIS, involving LNPs formulated with deuterated cationic lipid, provided compelling evidence of cationic lipid (CIL) fusion and molecule translocation across the ncSLB. However, uncertainties arise regarding lipid exchange and specific contributions of components. In this proposal we aim to address these uncertainties, to discern the influence of lipid exchange on LNP fusion and determine the structural changes in the ncSLB. Neutron Reflectivity study is expected to provide valuable insights into LNP behavior on a model endosome membrane, with potential implications for drug delivery applications

Experimental Report

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Data Citation

The recommended format for citing this dataset in a research publication is in the following format:

CARDENAS; DRDANOVSKI Jovana; EMILSSON Gustav; GVARAMIA Manuchar; HOOK Fredrik H; Nicolò Paracini; PARKKILA Petteri and Marianna Yanez Arteta. (2024). Unravelling LNP endosome escape. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-1035

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