转染
差示扫描量热法
层状结构
基因传递
信使核糖核酸
化学
胆固醇
脂滴
脂质双层
生物物理学
基因
生物化学
膜
生物
结晶学
热力学
物理
作者
Yulia Eygeris,Siddharth Patel,Antony Jozić,Gaurav Sahay
出处
期刊:Nano Letters
[American Chemical Society]
日期:2020-05-06
卷期号:20 (6): 4543-4549
被引量:239
标识
DOI:10.1021/acs.nanolett.0c01386
摘要
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.
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