Issue 28, 2023

Rational design and combinatorial chemistry of ionizable lipids for RNA delivery

Abstract

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.

Graphical abstract: Rational design and combinatorial chemistry of ionizable lipids for RNA delivery

Article information

Article type
Review Article
Submitted
27 mar 2023
Accepted
30 may 2023
First published
05 iyn 2023

J. Mater. Chem. B, 2023,11, 6527-6539

Rational design and combinatorial chemistry of ionizable lipids for RNA delivery

Y. Xu, A. Golubovic, S. Xu, A. Pan and B. Li, J. Mater. Chem. B, 2023, 11, 6527 DOI: 10.1039/D3TB00649B

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