Vector and cell engineering to increase productivity and stability of recombinant protein production in CHO cells

在进入临床和市场的新疗法中，生物制剂(蛋白质、抗体和疫苗)占了相当大的比例(7.5%)，并且份额不断增加(年增长20%)，取代了传统的小分子化合物；目前正在开发的所有药物中有33%是生物制剂(PharmaVision 2009)。提供新的生物药物疗法：挑战与机遇)。与疫苗和基因治疗产品一起，治疗性蛋白占FDA批准的治疗药物的一半。因此，我们见证了生物制品在最畅销的十大药物中的壮观出现。2000年，前10名中只有一种生物：促红细胞生成素。2014年的预测表明，前10名中将有7种生物制品：5种人源化抗体和2种重组蛋白(生物技术2010生命科学：适应成功，Burrill&Company)。因此，治疗性抗体及其衍生物占据了这个市场的最大份额。为了扩大其应用范围，需要对其进行重大改进，以降低其生产成本，同时提高其质量。因此，据估计，治疗性抗体的生产成本必须降低至少一个数量级，才能确保目前处于临床试验中的相当大一部分产品的经济可行性。因此，要提高高产克隆产生的效率，还有很多工作要做，我们将探索新的载体和细胞工程策略来实现这一目标。

Biologics (proteins, antibodies and vaccines) account for a significant (7.5%) and increasing share (20% annual growth) of new therapeutics entering the clinic and the market, displacing the traditional small-molecule chemical compounds; 33% of all drugs currently in development are biologics (PharmaVision 2009. Delivering New Biopharmaceutical Therapies: Challenges & Opportunities). Together with vaccines and gene therapy products, therapeutic proteins represent half of the FDA-approved therapeutics in the pipeline. As a result, we are witnessing a spectacular emergence of biologics in the top 10 most selling drugs. In 2000, there was only one biologic in the top 10: erythropoietin. The forecast for 2014 indicated that there would be 7 biologics in the top 10: 5 humanized antibodies and 2 recombinant proteins (Biotech 2010 Live Sciences: Adapting for success, Burrill & Company). Hence, therapeutic antibodies and derivatives thereof have the lion's share of this market. In order to expand their applications, significant improvements are required to lower their production costs while improving their quality. Thus, it is estimated that the cost of production of therapeutic antibodies must be reduced by at least one order of magnitude in order to ensure economic viability of a significant proportion of the products currently in clinical trials. Therefore much remains to be done to improve the efficiency of high-producing clones generation and we will explore new vector and cell engineering strategies toward that goal.