[疫苗技术的新希望:信使核糖核酸疫苗]

[New Hopes in Vaccine Technology: mRNA Vaccines].

作者信息

Yılmaz Engin

机构信息

Hacettepe University Faculty of Medicine, Department of Medical Biology, Emeritus, Ankara, Turkey.

出版信息

Mikrobiyol Bul. 2021 Apr;55(2):265-284. doi: 10.5578/mb.20219912.

Abstract

The major disadvantages of traditional virus vaccines are time constraints in development and difficulties in large-scale production. Therefore, there is a need to develop stronger and more versatile vaccine platforms. mRNA vaccines constitute a promising alternative to traditional vaccine approaches due to their high potential, rapid development capacity, low cost production and safe administration potential. Stability and translation of mRNA are crucial for a successful RNA vaccine. It is critical to determine mRNA purity, stability, and protein yield during the translation process. Therefore, engineering the RNA sequence, such as modification of the 5' cap structure, extension of the poly (A) tail, editing nucleotide sequences in non-coding (UTR) and coding (ORF) regions, or incorporating modified nucleotides into the structure, makes synthetic mRNA more translatable. Two classes of non-replicating and self-amplifying mRNA are used as vaccines. While non-replicating mRNA only encodes protein antigens of interest, self-amplifying mRNA also encodes proteins required for RNA replication. The transfer and formulation of mRNA vaccines to cells is crucial for determining the kinetics of antigen expression, protein amount, and strength of immune response. In order to achieve this success, mRNA vaccines are given to cells in various formats such as lipid nanoparticles, polymers, peptides, and naked mRNA to develop the most effective transfer material. Recent technological advances have eliminated the low efficiency in in vivo transfer and translation and have made this vaccine platform widespread in preclinical and clinical trials against various infectious diseases and cancers. Over the past decade, major technological innovations have made mRNA a promising therapeutic tool in the fields of vaccine development and protein replacement therapy. Nowadays, antigens, neutralizing antibodies and proteins with immunostimulating activity have become coded by mRNA vaccines. Although many mRNA vaccines appear to be effective in preclinical and clinical studies, there are still some issues to be improved in terms of transfer efficiency, targeting to specific cell types, and the reliability of transfer devices. In this review, the latest developments and current challenges in the optimization, formulation and transfer of mRNA vaccines to cells with future development perspectives have been reviewed.

摘要

传统病毒疫苗的主要缺点是开发过程中的时间限制以及大规模生产的困难。因此,需要开发更强大、更通用的疫苗平台。mRNA疫苗由于其潜力高、开发速度快、生产成本低以及给药安全性高,构成了传统疫苗方法的一个有前途的替代方案。mRNA的稳定性和翻译对于成功的RNA疫苗至关重要。在翻译过程中确定mRNA的纯度、稳定性和蛋白质产量至关重要。因此,对RNA序列进行工程改造,如修饰5'帽结构、延长聚(A)尾、编辑非编码(UTR)和编码(ORF)区域的核苷酸序列,或将修饰的核苷酸纳入结构中,可使合成mRNA更易于翻译。两类非复制型和自我扩增型mRNA被用作疫苗。非复制型mRNA仅编码感兴趣的蛋白质抗原,而自我扩增型mRNA还编码RNA复制所需的蛋白质。mRNA疫苗向细胞的传递和制剂对于确定抗原表达动力学、蛋白量和免疫反应强度至关重要。为了实现这一成功,mRNA疫苗以脂质纳米颗粒、聚合物、肽和裸mRNA等多种形式递送至细胞,以开发最有效的传递材料。最近的技术进步消除了体内传递和翻译的低效率,并使该疫苗平台在针对各种传染病和癌症的临床前和临床试验中广泛应用。在过去十年中,重大技术创新使mRNA成为疫苗开发和蛋白质替代疗法领域有前途的治疗工具。如今,抗原、中和抗体和具有免疫刺激活性的蛋白质已由mRNA疫苗编码。尽管许多mRNA疫苗在临床前和临床研究中似乎有效,但在传递效率、靶向特定细胞类型以及传递装置可靠性方面仍有一些问题有待改进。在这篇综述中,对mRNA疫苗向细胞的优化、制剂和传递方面的最新进展以及当前挑战进行了综述,并展望了未来的发展前景。

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