Recombinant Human Serum Albumin for Use in Cell Culture

描述（由申请人提供）：血浆来源的人血清白蛋白（pHSA）或牛血清白蛋白通常添加到基于细胞培养的疫苗和治疗生产中使用的细胞培养基中，因为它可以增强细胞生长并提高蛋白质产量。然而，pHSA的使用有传播病毒和新出现的传染性病原体的风险，特别是对那些没有检测方法的人。由于每年有数百万人使用基于细胞培养的疫苗进行免疫接种，还有数百万人需要基于细胞培养的治疗方法来治疗各种疾病，监管机构呼吁在疫苗和治疗生产中用重组人造血蛋白sa （rHSA）取代pHSA。在I期可行性研究中，我们发现来自水稻的rHSA不仅可以取代pHSA，而且在细胞生长增强方面比pHSA高出51%，在抗体产生方面比pHSA高出50%。在II期，我们将扩展I期的研究，在商业培养基的更大规模细胞培养中测试rHSA对杂交瘤、CHO和Vero细胞生长和生产力的影响。我们还将尝试确定哪些因素导致我们从大米中制备的rHSA具有优异的性能。我们将启动一个育种计划来提高粮食产量，从而进一步降低rHSA生产的成本。我们预计，在II期研究结束时，我们的项目将通过向市场提供性能优越的rHSA，满足监管机构对疫苗和治疗生产中pHSA的安全替代品的要求。公共卫生相关性：存在使用血浆来源的人血清白蛋白（pHSA）和血液制品作为细胞培养基成分用于细胞基疫苗和治疗性生产的新出现的传染性病原体在人与人之间传播的安全问题。监管机构已经要求用重组HSA取代pHSA。因此，在水稻中生产一种廉价的重组HSA来源，不仅可以确保安全替代pHSA，而且还可以使以细胞为基础的疫苗和疗法的生产具有成本效益。

DESCRIPTION (provided by applicant): Plasma-derived human serum albumin (pHSA) or bovine serum albumin are commonly added to cell culture media used in cell culture-based vaccine and therapeutic production, because it enhances cell growth and increases protein productivity. However, the use of pHSA carries the risk of transmission of viruses and emerging infectious pathogens, particularly for those for which no tests are available. Because millions of people are immunized annually with cell culture- based vaccines and millions more require cell culture-based therapeutics for the treatment of various disorders, regulatory agencies have called for a replacement of pHSA in vaccine and therapeutic production with recombinant HSA (rHSA). In Phase I feasibility study, we showed that rHSA from rice can not only be used to replace pHSA but also outperform pHSA by 51% in cell growth enhancement and by 50% in antibody production. In phase II, we will extend the studies in phase I to test the effect of rHSA on cell growth and productivity of hybridoma, CHO and Vero cells in larger scale cell culture with commercial media. We will also attempt to identify which factor(s) is (are) responsible for the superior performance of our rHSA preparation from rice. We will initiate a breeding program to improve the grain yield so to further reduce cost rHSA production. We anticipate that at the end of phase II studies, our project will have addressed the call by regulatory agencies for a safe alternative to pHSA in vaccine and therapeutic production by providing to the market rHSA with superior performance. Public Health Relevance: Safety concerns regarding human-to-human transmission of emerging infectious pathogens from the use of plasma-derived human serum albumin (pHSA) and blood products as an ingredient in cell culture media for cell-based vaccine and therapeutic production exist. Regulatory agencies have called for the replacement of pHSA with recombinant HSA. In response, an inexpensive source of recombinant HSA produced in rice would not only assure a safe alternative to pHSA, but would also allow cost- effective production of cell-based vaccine and therapeutics.