武学前沿｜研究人员致力于利用合成生物学促进细胞系的生产

来自英国的研究人员正在努力通过改变蛋白质的调节方式，来促进一种常见的生物制造细胞类型的蛋白质分泌。曼彻斯特生物技术研究所的助理研究员Mauro Torres博士正在试图修改调节转录因子，以帮助增加中国仓鼠卵巢（CHO）细胞在生物反应器中产生的蛋白质产物的数量。

Researchers from the U.K. are working to boost protein secretion in a common biomanufacturing cell type by changing how the proteins are regulated. Mauro Torres, PhD, a research associate from the Manchester Institute of Biotechnology, is modifying regulatory transcription factors to help increase the amount of protein product produced in a bioreactor by Chinese Hamster Ovary (CHO) cells.

据Torres说：“在过去的二三十年里，在如何修改细胞培养方面有了很大的进步，例如营养物质、增加细胞内的基因拷贝数，但有一件事是缺乏的，那就是细胞机制如何处理这些改进。”

According to Torres, “During the last twenty or thirty years, there’s been a major improvement in how you can modify the [cell] culture, such as […] the nutrients, [and increase] the gene copy number within the cells, but one thing that’s lacking is how the cellular machinery can handle these improvements.”

Torres解释说，生产过程中的许多改进，例如生物反应器中营养物质的混合方式，对CHO细胞来说可能是一种压力。他的研究灵感来自于如何通过基因工程使细胞更有弹性。

Many improvements in manufacturing, such as how the nutrient mix in the bioreactor, can be stressful for CHO cells, Torres explains. The inspiration for his research was how to make the cells more resilient by using genetic engineering.

Torres正在使用转录因子来激活或抑制某些基因，包括那些可以增加蛋白质产量的基因。他解释说，他设计了一种载体，可以将其引入细胞中，以观察它们是否过度表达一种蛋白质。

Torres is using transcription factors to activate or suppress certain genes, including those that can increase protein production. He explains that he designs a vector that can be introduced into cells to see whether they overexpress a protein.

他提到：“CHO细胞允许插入载体。”该团队使用电穿孔或化学物质将重组基因通过细胞膜扩散。研究人员希望，在未来，可以使用合成生物学对CHO细胞进行工程改造以满足特定目的，例如具有可用于连续流工艺的功能。

“CHO cells are permissive to the insertion of vectors,” he says, and the team used electroporation or chemicals to diffuse the recombinant gene through the cell membrane. The researchers hope that, in the future, CHO cells may be engineered using synthetic biology to meet a specific purpose, such as with features useful for continuous processing.

正如Torres解释的那样，合成生物学可用于创建一个新的表达系统，例如由多西环素调节。这意味着基因的表达量可以被打开和关闭，或精确控制。

As Torres explains, synthetic biology can be used to create a new expression system regulated by, for example, doxycycline. This means that the amount of gene expression can be switched on and off, or precisely controlled.

他表示：“你可以设计出所有功能都可控的细胞，并且可以问这样的问题：你如何在设计细胞时考虑到最终的用途/产品？”

“You can design cells with all features controllable,” he says. “And can ask the question: how do you design cells with the end [use/product] in mind?”

原文链接：

https://www.genengnews.com/topics/bioprocessing/researchers-work-to-boost-cell-line-production-with-synthetic-biology/

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