Expression of Human Transferrin in Rice Grain

产品描述（申请人提供）：转铁蛋白是细胞培养基中的一种重要成分，因为其在调节细胞铁摄取、转运和利用方面具有关键作用，也是一种有前途的药物载体，通过其独特的转铁蛋白受体介导的内吞途径增加药物治疗指数。目前使用的转铁蛋白主要由血浆制成，因此当面临血液供应短缺时，它具有被血液传播的病原体污染的高风险。转铁蛋白的重组生产理想地解决了用于细胞培养和药物递送市场的天然转铁蛋白的安全性问题和短缺问题。目前，在细胞培养市场上，只有有限数量的酵母细胞表达的重组人转铁蛋白可以以极高的价格获得。Ventria Bioscience已经在大米中大规模生产了人乳铁蛋白，这是一种与人转铁蛋白密切相关的蛋白。在本研究中，我们计划利用类似于大规模生产乳铁蛋白的技术，在水稻中表达人转铁蛋白。拟议的研究将开发稳定的转基因水稻品系，表达重组人转铁蛋白，作为一种安全和低成本的替代人血来源的转铁蛋白，用于生物制药细胞培养和药物输送市场。公共卫生相关性：转铁蛋白在调节铁中起着至关重要的作用，是细胞培养基中使用的重要成分，也是药物缀合物的潜在候选者。细胞培养中使用的转铁蛋白目前由血浆制成，因此具有被病原体污染的高风险。开发负担得起的无动物来源的重组人转铁蛋白将使得转铁蛋白在细胞培养和药物缀合物中的安全大规模使用成为可能。

DESCRIPTION (provided by applicant): Transferrin is an essential ingredient used in cell culture media due to its crucial role in regulating cellular iron uptake, transport, and utilization, and also a promising drug carrier to increase drug therapeutic index via its unique transferrin receptor-mediated endocytosis pathway. Transferrin currently in use is made mainly from blood plasma, and thus it carries a high risk of contamination with blood-borne pathogens while facing blood supply shortage. Recombinant production of transferrin protein is ideally situated to address both the safety concern and shortage problem of native transferrin for use in cell culture and drug delivery markets. Currently only limited quantity of yeast cell-expressed recombinant human transferrin is available at an extremely high price in the cell culture market. Ventria Bioscience already has produced the human lactoferrin, a close relative to human transferrin, in rice grains on large scale and at low lost. In this proposal, we plan to exploit similar technology used for large scale production of lactoferrin to express human transferrin in rice grains. The proposed studies will develop stable transgenic rice lines expressing recombinant human transferrin as a safe and low cost alternative to human blood derived transferrin for use in biopharmaceutical cell culture and drug delivery markets. Public Health Relevance: Transferrin plays a crucial role in regulating iron and is an essential ingredient used in cell culture medium and a potential candidate for drug conjugates. Transferrin used in cell culture is currently made from blood plasma, and thus carries a high risk of contamination with pathogens. Development of an affordable animal free source of recombinant human transferrin would enable safe large scale use of transferrin in cell culture and drug conjugates.