Ionizable Lipid Nanoparticles for mRNA Delivery

Author:

Tang Xuefeng1,Zhang Ying2,Han Xiaojun1ORCID

Affiliation:

1. State Key Laboratory of Urban Water Resource and Environment School of Chemistry and Chemical Engineering Harbin Institute of Technology Harbin 150001 China

2. College of Materials and Chemical Engineering Heilongjiang Institute of Technology Harbin 150050 China

Abstract

Therapeutics based on messenger RNA (mRNA) have become a promising class of methods for various diseases’ treatments in recent years. The safe and effective delivery of mRNA into target cells is the premise of the clinical translation of mRNA. Due to the protonation of ionizable lipids in acidic conditions, the ionizable lipid nanoparticles (iLNPs) have lower toxicity and higher endosomal escape efficiency than permanent cationic lipid nanoparticles (cLNPs). They not only exhibit excellent delivery ability in commercial COVID‐19 mRNA vaccines but also are highly potential carriers for delivering mRNA drugs. This review summarizes the composition, preparation, stability of mRNA iLNPs, and the recent progress in the mRNA delivery by iLNPs. According to the structure characteristics of ionizable heads, the ionizable lipids are classified into tertiary amine, quaternary amine, imidazole core, piperidine core, piperazine core, and diketopiperazine core‐based head lipids. Their design, optimization, and applications on mRNA delivery are discussed. The current status of representative clinical trials based on mRNA iLNPs delivery is also analyzed. The challenges and prospects of mRNA iLNPs delivery in clinical applications are proposed at the end.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Heilongjiang Province

Publisher

Wiley

Subject

General Medicine

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