The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Roslin Technologies Limited, Roslin Innovation Centre, Easter Bush Campus, Midlothian, EH25 9RG, UK.
BMC Biotechnol. 2018 Dec 29;18(1):82. doi: 10.1186/s12896-018-0495-1.
The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside of the US market, is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins to be produced by genetically-modified animals; several therapeutic proteins from such animal bioreactors are already on the market after successful clinical trials and regulatory approval. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture-based production systems. This could lead to more affordable treatments and wider markets, including in developing countries and for animal health applications.
Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, we describe the expression, purification and functional characterization of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1.
Our work optimizes and validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications.
蛋白质类药物的全球市场是所有药物类别中复合年增长率最高的,但与传统化学药物相比,其制造和验证成本较高,因此其在除美国市场以外的市场的供应情况受到影响。转基因技术的进步使得有价值的蛋白质可以通过基因修饰的动物来生产;经过成功的临床试验和监管批准后,已经有几种来自此类动物生物反应器的治疗性蛋白质投放市场。尽管具有许多潜在优势,但由于历史上生产转基因鸟类的困难,鸡在生物反应器开发方面落后于哺乳动物,但与传统的基于细胞培养的生产系统相比,在转基因鸡的蛋清中生产治疗性蛋白质将大大降低整个生产周期的成本。这可能会带来更实惠的治疗方法和更广阔的市场,包括发展中国家和动物保健应用。
我们在这里报告了高效生成新的转基因鸡系以优化鸡蛋中蛋白质生产的方法。作为概念验证,我们描述了三种药物蛋白,即人细胞因子干扰素 α2a 和两种细胞因子 CSF1 的特异性 Fc 融合蛋白的表达、纯化和功能特征。
我们的工作优化并验证了一种转基因鸡系统,用于以具有成本效益的方式生产用于治疗和其他应用的纯、高质量、生物活性蛋白。