Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery.

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ID: 106259
2020
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Abstract
Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to C24 alkyl tail of cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol) while the addition of double bond induces lipid partitioning (>90% increase compared to cholesterol. LNPs with multilamellar and faceted structures, as well as lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design towards enhanced gene delivery.
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eygeris2020deconvolutingnano Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Eygeris, Yulia;Patel, Siddharth;Jozic, Antony;Sahay, Gaurav;
Journal Nano letters
Year 2020
DOI
10.1021/acs.nanolett.0c01386
URL
Keywords
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