May 06, 2020
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 a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.
Publication - Abstract
Nov 30, 2019
Journal of Controlled Release
Publication - Summary
Dec 16, 2016
Angewandte Chemie International Edition
The CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein) gene-editing tool allows for sequence-specific cuts to genomic DNA, which can result in permanent silencing of a gene, or replacement of gene sequen...