Hormone-medicated improvement of recombinant protein yields in plants

近年来，由于第一种用于人类治疗的植物制成的生物制药获得批准，在最近的埃博拉病毒爆发期间，证明了在植物中容易产生治疗性抗体的可行性，以及越来越多的植物制成的蛋白质正在进行I期或II期临床试验，支持了将植物用作生物工厂来生产临床上有用的重组蛋白。该项目的目标是调节烟草的激素代谢，这是一个很有前途的表达平台，在降低叶片中自然丰富的蛋白质污染物的同时，提高重组蛋白的产量。将进行实验，以评估外源激素处理的潜力，使用商业生产装置中应用的一些天然和合成化学品来控制植物的生长和发育。实验将与荷尔蒙诱导的“辅助转基因”并行进行，以评估通过基因重现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，与免疫和炎症疾病有关的模型糖蛋白，以及用于生产流感vaccines.**********************************************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.**********************************************