Negatively charged phospholipids doped liposome delivery system for mRNA with high transfection efficiency and low cytotoxicity
Lin Wang,
Huanchun Xing,
Shuai Guo,
Wenbin Cao,
Zinan Zhang,
Lijuan Huang,
Sui Xin,
Yuan Luo,
Yongan Wang,
Jun Yang
Affiliations
Lin Wang
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Huanchun Xing
Tianjin University of Science and Technology, Tianjin, China
Shuai Guo
Hebei University of Science and Technology, Shijiazhuang, China
Wenbin Cao
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Zinan Zhang
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Lijuan Huang
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Sui Xin
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Yuan Luo
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Yongan Wang
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
Jun Yang
State Key Laboratory of Toxicology and Medical Countermeasures, Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China
AbstractMessenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major challenge. Appropriate delivery system (DS) determines the final effect of mRNA. Cationic lipids play a crucial and decisive role in the entire DS, but also cause huge biosafety problems due to the high toxicity. In this study, a new DS for mRNA delivery that combines negatively charged phospholipids was developed in order to neutralize the positive charge and thus increase the safety. Further, the factors affecting mRNA transfection from cell to animal were investigated. The mRNA DS with optimum condition of lipid composition, proportions, structure, and transfection time was synthesized. Adding an appropriate amount of the anionic lipid to liposomes could increase the safety while maintaining the original transfection efficiency. For transporting mRNA in vivo, requirements regarding the mRNA encapsulation and releasing rate should be further considered to optimize DS design and preparation.
