Expression of Human Transferrin in Rice Grain

说明(申请人提供)：转铁蛋白是细胞培养液中的基本成分，因为它在调节细胞铁的吸收、运输和利用方面起着关键作用，也是一种很有前途的药物载体，通过其独特的转铁蛋白受体介导的内吞作用来提高药物治疗指数。目前使用的转铁蛋白主要是从血浆中提取的，因此在面临血液供应短缺的情况下，它具有被血液传播病原体污染的高风险。重组转铁蛋白的生产是解决天然转铁蛋白在细胞培养和药物输送市场中使用的安全性问题和短缺问题的理想选择。目前，酵母细胞表达的重组人转铁蛋白在细胞培养市场上的供应数量有限，价格极高。Ventria Bioscience已经在大米籽粒中大规模、低损失地生产了人类乳铁蛋白，这是一种与人类转铁蛋白关系密切的蛋白质。在这项提议中，我们计划利用类似的技术来大规模生产乳铁蛋白，在大米中表达人转铁蛋白。建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人血源性转铁蛋白替代品，用于生物制药细胞培养和药物输送市场。公共卫生相关性：转铁蛋白在调节铁的过程中起着至关重要的作用，是细胞培养液中的基本成分，也是药物结合物的潜在候选者。细胞培养中使用的转铁蛋白目前是由血浆制成的，因此具有很高的被病原体污染的风险。开发一种负担得起的无动物来源的重组人转铁蛋白将使转铁蛋白在细胞培养和药物结合物中安全、大规模地使用。

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.