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用于癌症基因治疗的mRNA疫苗的非病毒递送系统

Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy.

作者信息

Wang Yusi, Zhang Rui, Tang Lin, Yang Li

机构信息

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Pharmaceutics. 2022 Feb 25;14(3):512. doi: 10.3390/pharmaceutics14030512.

Abstract

In recent years, the use of messenger RNA (mRNA) in the fields of gene therapy, immunotherapy, and stem cell biomedicine has received extensive attention. With the development of scientific technology, mRNA applications for tumor treatment have matured. Since the SARS-CoV-2 infection outbreak in 2019, the development of engineered mRNA and mRNA vaccines has accelerated rapidly. mRNA is easy to produce, scalable, modifiable, and not integrated into the host genome, showing tremendous potential for cancer gene therapy and immunotherapy when used in combination with traditional strategies. The core mechanism of mRNA therapy is vehicle-based delivery of in vitro transcribed mRNA (IVT mRNA), which is large, negatively charged, and easily degradable, into the cytoplasm and subsequent expression of the corresponding proteins. However, effectively delivering mRNA into cells and successfully activating the immune response are the keys to the clinical transformation of mRNA therapy. In this review, we focus on nonviral nanodelivery systems of mRNA vaccines used for cancer gene therapy and immunotherapy.

摘要

近年来,信使核糖核酸(mRNA)在基因治疗、免疫治疗和干细胞生物医学领域的应用受到广泛关注。随着科学技术的发展,mRNA在肿瘤治疗中的应用已趋于成熟。自2019年严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染爆发以来,工程化mRNA和mRNA疫苗的研发迅速加速。mRNA易于生产、可扩展、可修饰且不整合到宿主基因组中,与传统策略联合使用时,在癌症基因治疗和免疫治疗中显示出巨大潜力。mRNA治疗的核心机制是基于载体将体外转录的mRNA(IVT mRNA)递送至细胞质中,IVT mRNA体积大、带负电荷且易降解,随后表达相应的蛋白质。然而,有效地将mRNA递送至细胞内并成功激活免疫反应是mRNA治疗临床转化的关键。在本综述中,我们重点关注用于癌症基因治疗和免疫治疗的mRNA疫苗的非病毒纳米递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c4/8949480/1de7a8b7c21e/pharmaceutics-14-00512-g001.jpg

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