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| Gene Strategies of Enhancing the Anti-apoptosis Ability of Mammalian Cell in Engineering |
| XU Hong-ji, ZHANG Bing-bing |
| Bioengineering College, Chongqing University, Chongqing 400030, China) (Key Laboratory of Biorheological Science and Technology, Chongqing University, Ministry of Education, Chongqing 400030, China |
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Abstract Mammalian cells have significant advantages in producing recombinant protein drugs, which make it widely used in industry. In the process of production, however, environmental stress, which can result from nutrient depletion and by-product accumulation, activates apoptosis through signalling cascades regulators. It is the burden of improving the protein production that have the cell more susceptible to apoptosis, decreasing bioreactor performance and hindering large-scale production. Therefore,apoptosis, programed cell death, seriously limits the recombinant protein production, and how to improve the anti-apoptotic ability of engineering cells has accordingly become a hot point that attracted the attention of biologists all over the world. Apoptosis, as well as proliferation and differentiation, is one of the biological processes that cell must experience. With the understanding of the mechanism of apoptosis and revealing of many apoptosis genes in previous studies, a variety of anti-apoptotic approaches were found which is helpful to inhibit apoptosis and to enhance the robustness, survival and productivity of production cell lines. The anti-apoptotic approaches commonly used in engineering include: lowering apoptotic proteins, increasing anti-apoptotic proteins, over-expressing growth factor and insuin-like growth factor and modifying the intracellular enzyme related to metabolism in order to prevent the toxic metabolites from accumulating. Although the resistance of cell to apoptosis were, to some extent, improved by the strategies mentioned above, it is very essential for biotechnologists to search for more effective anti-apoptotic approaches that could lead to the greatest improvements in cell survival, provide unequalled bioreactor performance and enhance biopharmaceutical productivities.
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Received: 28 March 2012
Published: 25 June 2012
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