Rational design and combinatorial chemistry of ionizable lipids for RNA delivery

In 2018, LNPs enabled the first FDA approval of a siRNA drug (Onpattro); two years later, two SARS-CoV-2 vaccines (Comirnaty, Spikevax) based on LNPs containing mRNA also arrived at the clinic, saving millions of lives during the COVID-19 pandemic. Notably, each of the three FDA-approved LNP formula...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2023-07, Vol.11 (28), p.6527-6539
Main Authors: Xu, Yue, Golubovic, Alex, Xu, Shufen, Pan, Anni, Li, Bowen
Format: Article
Language:English
Subjects:
Cholesterol
Combinatorial analysis
Combinatorial chemistry
COVID-19
COVID-19 Vaccines
Humans
Lipids
Lipids - chemistry
mRNA
Nanoparticles - chemistry
Pandemics
RNA, Messenger - genetics
SARS-CoV-2 - genetics
Severe acute respiratory syndrome coronavirus 2
siRNA
Vaccines
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Summary:In 2018, LNPs enabled the first FDA approval of a siRNA drug (Onpattro); two years later, two SARS-CoV-2 vaccines (Comirnaty, Spikevax) based on LNPs containing mRNA also arrived at the clinic, saving millions of lives during the COVID-19 pandemic. Notably, each of the three FDA-approved LNP formulations uses a unique ionizable lipid while the other three components, i.e. , cholesterol, helper lipid, and PEGylated lipid, are almost identical. Therefore, ionizable lipids are critical to the delivery efficiency of mRNA. This review covers recent advances in ionizable lipids used in RNA delivery over the past several decades. We will discuss chemical structures, synthetic routes, and structure-activity relationships of ionizable lipids. This review will delve into the crucial role of ionizable lipids in the development of lipid nanoparticles (LNPs) for efficient RNA delivery.
ISSN:2050-750X
2050-7518
DOI:10.1039/d3tb00649b