Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery.
Nano Lett
; 20(6): 4543-4549, 2020 06 10.
Article
in English
| MEDLINE | ID: covidwho-636626
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 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
RNA, Messenger
/
Drug Carriers
/
Viral Vaccines
/
Cholesterol
/
Coronavirus Infections
/
Nanoparticles
/
Pandemics
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Nano Lett
Year:
2020
Document Type:
Article
Affiliation country:
Acs.nanolett.0c01386
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