基因编辑在构建抗凋亡工程细胞中的应用

The Application of Genome Editing in the Construction of Anti-Apoptotic Engineering Cells

21世纪以来,人们在生物科技领域取得了长足进步。一方面,基因编辑技术的问世为精确修饰目的基因带来可能,即能够在活细胞中完成特定DNA片段的插入、删除、替换、激活、抑制等任务;另一方面,越来越多的新型重组蛋白药物被开发并应用于对抗肿瘤等人类重大疾病,相比于传统化学药物,它具有高特异性和低副作用等显著优势,治疗效果得到普遍认可。目前用于生产治疗性重组蛋白的工程细胞株主要来源于哺乳动物,然而,由于生产过程中任何环境因素的改变都可能使工程细胞凋亡,严重影响蛋白的表达水平,因此大大提高了生产成本。研究人员在明确工程细胞的生长与死亡相关机制后,利用基因编辑技术对其进行了定向改造,提高了其表达水平。该文就对该方面研究成果进行了综述。

Since the 21 st century, people have made great progress in the field of biotechnology. The advent of genome editing technology brings possibility to precisely modify target genes, which means we can perform certain tasks in living cells like inserting, deleting, replacing, activating or suppressing specific DNA fragments. Furthermore, more and more new recombinant protein drugs have been developed for combating severe diseases such as cancers. Compared with traditional chemical drugs, it has significant advantages such as high specificity and low side effects. Besides, its therapeutic effect has been widely recognized. Currently, the engineering cell lines used for the production of therapeutic recombinant proteins are mainly derived from mammal cells. However, due to various environmental factors in the production process, the apoptosis rate of engineering cell is extremely high, which seriously affects the expression level of the proteins, resulting in greatly increasing the production costs. After clarifying the mechanisms involved in the growth and death of cells, researchers, by utilizing genome editing technology, modified cells to improve the expression level. Here we attempt to summarize the research results in this field.