期刊
JOURNAL OF CONTROLLED RELEASE
卷 338, 期 -, 页码 537-547出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.08.061
关键词
mRNA therapy; Polymeric micelle; Immune response
资金
- National Natural Science Foundation of China [81830101]
- National Science and Technology Major Project [2017ZX09303013-003]
A novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) was designed for mRNA delivery. In vitro experiments showed high transfection efficiencies and low cytotoxicity of PVES compared to PEI 25k. Mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and showed no obvious toxicity.
mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.
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