DOI > 10.5291/ILL-DATA.9-13-909

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Title

Lipid nanoparticles-Apolipoprotein E interaction: the role of pH

Abstract

Therapeutic treatments based on the protein production by delivering messenger RNA (mRNA) represent a promising approach. One of the major challenges is to protect mRNA from enzymatic degradation and deliver it into the target cells. Lipid nanoparticles (LNPs) formed by a cationic ionizable lipid (CIL), DSPC, cholesterol and a pegylated lipid were approved for delivery of small interference RNA. There are still concerns about how to improve LNP efficacy following endocytosis. The bio-distribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNPs administration, e.g. ApolipoproteinE (ApoE). ApoE has been identified as fundamental regarding the efficacy of siRNA-LNPs but its effect on the LNP structure and subsequently endosomal escape has not been studied. Our recent results suggest that ApoE binding affect the LNP structure at pH 7.4. We aim to characterise the LNP structure at pH conditions relevant to different endosomal compartments, and investigate not only how ApoE binding is regulated by the LNP surface structure but more importantly how the LNP overall structure responds to ApoE binding.

Experimental Report

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Data Citation

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

SEBASTIANI Federica; CARDENAS; PORCAR Lionel; Sarah Waldie and Marianna Yanez Arteta. (2020). Lipid nanoparticles-Apolipoprotein E interaction: the role of pH. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-909

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