The role of lipid components in lipid nanoparticles for vaccines and gene therapy

被引：586

作者：

Albertsen, Camilla Hald ^{[1
]}

Kulkarni, Jayesh A. ^{[2
]}

Witzigmann, Dominik ^{[2
]}

Lind, Marianne ^{[1
]}

Petersson, Karsten ^{[1
]}

Simonsen, Jens B. ^{[1
]}

机构：

[1] LEO Pharm AS, Explorat Formulat & Technol, CMC Design & Dev, Industriparken 55, DK-2750 Ballerup, Denmark

[2] NanoVat Therapeut Inc, 2405 Wesbrook Mall, 4th Floor, Vancouver V6T 1Z3, BC, Canada

来源：

ADVANCED DRUG DELIVERY REVIEWS | 2022年 / 188卷

关键词：

Lipid nanoparticles; LNP; Ionizable lipid; PEGylated lipid; Helper lipid; Nucleic acid; Physicochemical properties; pK a; Drug delivery; Targeting; PEGYLATED LIPOSOMAL DOXORUBICIN; ACCELERATED BLOOD CLEARANCE; MESSENGER-RNA; IN-VIVO; CATIONIC LIPIDS; INTRACELLULAR DELIVERY; REPEATED INJECTIONS; SIRNA DELIVERY; PLASMID; FORMULATIONS;

D O I：

10.1016/j.addr.2022.114416

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Lipid nanoparticles (LNPs) play an important role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro (R), highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand what is key to the success of LNPs, we need to understand the role of the building blocks that constitute them.In this Review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulation efficiency, cellular uptake, and endosomal escape. To explore this, we present findings from the liposome field as well as from landmark and recent articles in the LNP literature. We also discuss challenges and strategies related to in vitro/in vivo studies of LNPs based on fluorescence readouts, immunogenicity/reactogenicity, and LNP delivery beyond the liver. How these fundamental challenges are pursued, including what lipid components are added and combined, will likely determine the scope of LNP-based gene therapies and vaccines for treating various diseases.(c) 2022 Elsevier B.V. All rights reserved.

引用

页数：17

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