由VSW - 3 RNA聚合酶产生的信使核糖核酸（mRNA）具有高水平的翻译效率且炎症刺激较低。
mRNA produced by VSW-3 RNAP has high-level translation efficiency with low inflammatory stimulation.
作者信息
Wang Guoquan, Cheng Rui, Chen Qiubing, Xu Yuandong, Yu Bingbing, Zhu Bin, Yin Hao, Xia Heng
机构信息
Department of Urology, Frontier Science Centre for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Key Laboratory of Molecular Biophysics, The Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Cell Insight. 2022 Sep 6;1(5):100056. doi: 10.1016/j.cellin.2022.100056. eCollection 2022 Oct.
preparation of mRNA is a key step for mRNA therapeutics. The widely used T7 RNA polymerase (RNAP) was shown to have many by-products during transcription (IVT) process, among which double-stranded RNA (dsRNA) is the major by-product to activate the intracellular immune response. Here, we describe the use of a new VSW-3 RNAP that reduced dsRNA production during IVT and the resulting mRNA exhibited low inflammatory stimulation in cells. Compared to T7 RNAP transcripts, these mRNA exhibited superior protein expression levels, with an average of 14-fold increase in Hela cells and 5-fold increase in mice. In addition, we found that VSW-3 RNAP did not require modified nucleotides to improve protein production of IVT products. Our data suggest that VSW-3 RNAP could be a useful tool for mRNA therapeutics.
信使核糖核酸（mRNA）的制备是mRNA疗法的关键步骤。广泛使用的T7 RNA聚合酶（RNAP）在体外转录（IVT）过程中会产生许多副产物，其中双链RNA（dsRNA）是激活细胞内免疫反应的主要副产物。在此，我们描述了一种新型VSW-3 RNAP的使用，它在IVT过程中减少了dsRNA的产生，并且所得的mRNA在细胞中表现出低炎症刺激。与T7 RNAP转录本相比，这些mRNA表现出更高的蛋白质表达水平，在Hela细胞中平均增加了14倍，在小鼠中增加了5倍。此外，我们发现VSW-3 RNAP不需要修饰核苷酸来提高IVT产物的蛋白质产量。我们的数据表明，VSW-3 RNAP可能是mRNA疗法的一种有用工具。
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