期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 8, 期 -, 页码 459-468出版社
CELL PRESS
DOI: 10.1016/j.omtn.2017.07.013
关键词
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资金
- German research association (Deutsche Forschungsgemeinschaft)
- National Health and Medical Research Council Principal Research Fellowship
- National Heart Foundation Postdoctoral Fellowship
- Paul Korner Innovation Award
- Margarete von Wrangell Habilitation Programme for Women of the Ministry of Science and Arts Baden-Wuerttemberg
Synthetically modified mRNA is a unique bioactive agent, ideal for use in therapeutic applications, such as cancer vaccination or treatment of single-gene disorders. In order to facilitate mRNA transfections for future therapeutic applications, there is a need for the delivery system to achieve optimal transfection efficacy, perform with durable stability, and provide drug safety. The objective of our study was to comprehensively analyze the use of 3 beta-[N-( N', N'-dimethylaminoethane) carbamoyl](DC-Cholesterol)/dioleoylphosphatidylethanolamine (DOPE) liposomes as a potential transfection agent for modified mRNAs. Our cationic liposomes facilitated a high degree of mRNA encapsulation and successful cell transfection efficiencies. More importantly, no negative effects on cell viability or immune reactions were detected post-transfection. Notably, the liposomes had a long-acting transfection effect on cells, resulting in a prolonged protein production of alpha-1-antitrypsin (AAT). In addition, the stability of these mRNA-loaded liposomes allowed storage for 80 days, without the loss of transfection efficacy. Finally, comprehensive analysis showed that these liposomes are fully hemocompatible with fresh human whole blood. In summary, we present an extensive analysis on the use of DC-cholesterol/DOPE liposomes as mRNA delivery vehicles. This approach provides the basis of a safe and efficient therapeutic strategy in the development of successful mRNA-based drugs.
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