Ionizable Lipids with Triazole Moiety from Click Reaction for LNP-Based mRNA Delivery

  • Molecules. 2023 May 12;28(10):4046. doi: 10.3390/molecules28104046.
Yixiang Wang  1 ,  Xiao Si  1 ,  Yi Feng  1 ,  Dan Feng  2 ,  Xiaoyu Xu  2 ,  Yan Zhang  1
Affiliations
  • 1. School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Jiangsu Key Laboratory of Advanced Organic Materials, State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University, Nanjing 210023, China.
  • 2. Nanjing Vazyme Biotechnology Company, Nanjing 210034, China.
PMID: 37241787 DOI: 10.3390/molecules28104046
Abstract

Ionizable lipid-containing lipid nanoparticles (LNPs) as a non-viral vector with good safety and potency have been considered as an ideal delivery system for gene therapy. The screening of ionizable lipid libraries with common features but diverse structures holds the promise of finding new candidates for LNPs to deliver different nucleic acid drugs such as messenger RNAs (mRNAs). Chemical strategies for the facile construction of ionizable lipid libraries with diverse structure are in high demand. Here, we report on the ionizable lipids containing the triazole moiety prepared by the copper-catalyzed alkyne-azide click reaction (CuAAC). We demonstrated that these lipids served well as the major component of LNPs, in order to encapsulate mRNA using luciferase mRNA as the model system. Thus, this study shows the potential of click chemistry in the preparation of lipid libraries for LNP assembly and mRNA delivery.

Keywords
click reaction; ionizable lipids; lipid nanoparticles; mRNA delivery.
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