Hormone-medicated improvement of recombinant protein yields in plants

近年来，植物作为生产临床上有用的重组蛋白的生物工厂的使用得到了支持，这是因为第一种植物制造的用于人类治疗的生物药物的批准，在最近的埃博拉病毒爆发期间，在植物中容易生产治疗性抗体的可行性得到了证实，以及越来越多的植物制造的蛋白正在进行I期或II期临床试验。该项目的目标是调节本氏烟草（Nicotiana benthamiana）的激素代谢，本氏烟草是一种有前途的表达平台，以这种方式提高重组蛋白产量，同时下调叶片中天然丰富的蛋白质污染物。将进行实验，以评估外源激素治疗的潜力，使用一些天然和合成化学品应用于商业生产设置，以控制植物生长和发育。实验将与诱导凋亡的“辅助转基因”平行进行，以评估遗传复制化学处理效果的可行性。这些提高植物重组蛋白产量的新方法将用不同的医学蛋白进行测试，包括用于控制心脏手术期间血液凝固的调节蛋白，参与免疫和炎症疾病的模型糖蛋白，以及用于生产流感疫苗的病毒抗原。

The use of plants as bio-factories for the production of clinically useful recombinant proteins has been bolstered in recent years by the approval of a first plant-made biopharmaceutical for human therapy, the demonstrated feasibility of readily producing therapeutic antibodies in plants during the recent Ebola virus outbreak, and the ever increasing number of plant-made proteins undergoing Phase I or Phase II clinical trials. The goal of this project is to modulate the hormonal metabolism of Nicotiana benthamiana, a promising expression platform, in such a way as to boost recombinant protein yields while downregulating naturally abundant protein contaminants in leaves. Experiments will be conducted to evaluate the potential of exogenous hormone treatments, using a number of natural and synthetic chemicals applied in commercial production setups to control plant growth and development. Experiments will be conducted in parallel with hormone-inducing "accessory transgenes" to assess the feasibility of genetically reproducing the effects of chemical treatments. These new ways of enhancing recombinant protein yield in plants will be tested with different proteins of medical interest, including a regulatory protein used to control blood coagulation during cardiac surgeries, a model glycoprotein involved in immune and inflammatory diseases, and a viral antigen for the production of flu vaccines.