Self-assembled polymeric micelle as a novel mRNA delivery carrier.

Self-assembled polymeric micelle as a novel mRNA delivery carrier.
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DOI:
10.1016/j.jconrel.2021.08.061
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发表时间:
2021-10-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Wang S
Wang S
中科院分区:
其他
文献类型:
--
作者:
Ren J;Cao Y;Li L;Wang X;Lu H;Yang J;Wang S

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基于mRNA的疗法已经在临床前和临床研究中进行了评估,用于治疗多种疾病,如癌症免疫疗法和传染病疫苗。然而,开发安全有效的给药系统仍然具有挑战性。在这里,我们设计了一种新的自组装聚合物胶束的基础上,维生素E琥珀酸酯改性聚乙烯亚胺共聚物(PVES)提供mRNA。PVES在体外可将mRNA转染HEK-293 T、HeLa和Vero等多种细胞系,转染效率明显高于PEI 25 k。此外,PVES的细胞毒性远低于PEI 25 k. PVES/SARS-CoV-2 mRNA疫苗经小鼠肌肉注射后,小鼠产生了较强的抗体应答,且无明显毒性反应。这些结果表明PVES作为mRNA的安全有效的递送载体的潜力。
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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