The Application of Lipid Nanoparticle-delivered mRNA in Disease Prevention and Treatment
10.16476/j.pibb.2024.0316
- VernacularTitle:脂质纳米颗粒递送mRNA在疾病防治中的应用
- Author:
Wei-Lun SUN
1
;
Ti-Qiang ZHOU
1
;
Hai-Yin YANG
1
;
Lu-Wei LI
2
;
Yu-Hua WENG
1
;
Jin-Chao ZHANG
2
;
Yuan-Yu HUANG
1
;
Xing-Jie LIANG
3
Author Information
1. School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China
2. College of Chemistry & Materials Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China
3. Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, National Center for Nanoscience and Technolgy, Beijing 100190, China
- Publication Type:Journal Article
- Keywords:
lipid nanoparticles;
mRNA;
engineering;
targeting
- From:
Progress in Biochemistry and Biophysics
2024;51(10):2677-2693
- CountryChina
- Language:Chinese
-
Abstract:
In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.
