Recombinant human serum albumin for therapeutic use

描述(由申请人提供)：由于混合供体血液分离产生的人血清白蛋白(HSA)存在潜在的疾病污染风险，以及治疗应用中对HSA的需求不断增加，生产重组人血清白蛋白(RHSA)作为血源性HSA的替代品已变得有吸引力。虽然在各种蛋白质表达系统，特别是在酵母中已经取得了显著的进展，但重组人血清白蛋白的生产成本非常高。由于资本需求较大，重组人血清白蛋白的生产规模有限，无法满足市场需求。Ventria Bioscience开发了一种专有的蛋白质表达系统ExpressTec，最近已用于在水稻籽粒中表达RHSA，表达水平为8g/kg面粉重(40%总可溶性蛋白质)，是其他表达系统的4~100倍。以低于0.22英镑/公斤的成本生产米粒，从而以0.04美元/克的价格生产从大米中提取的重组人血清白蛋白。这种替代重组人血清白蛋白的低成本产品很容易扩大规模。在这一阶段的SBIR建议中，我们计划发展一个纯合子系并对转基因植物进行鉴定。同时，我们将开发重组人血清白蛋白的纯化工艺，并从大米中制备重组人血清白蛋白。然后我们将进行体外蛋白质分析，比较重组人血清白蛋白和天然人血清白蛋白的生化和生物物理特性。在第二阶段，我们将生产大量的大米颗粒，并提纯足够数量的重组人血清白蛋白，用于模型动物和人体的临床前和临床试验。我们的长期目标是生产大量和高质量的重组人血清白蛋白，其成本与血液来源的人血清白蛋白相当，用于治疗应用。

DESCRIPTION (provided by applicant): Due to the potential risk of disease contamination of human serum albumin (HSA) derived from fractionation of pooled donor blood and the increasing demand of HSA in therapeutic applications, production of recombinant human serum albumin (rHSA) has become attractive as an alternative to blood-derived HSA. While significant progress has been made in various protein expression systems, particularly in yeast, the cost of rHSA production is very high. Due to a large capital requirement, the scale of rHSA production is limited and will not be able to meet the market demand. Ventria Bioscience has developed a proprietary protein expression system, ExpressTec, and has recently used it to express rHSA in rice grain with an expression level of 8 gram/kg flour weight (40% total soluble protein) which is 4 to 100 folds higher than other expression systems. Rice grain can be produced at cost of less than <0.22 /kg thus rHSA derived from rice can be produced at <$0.04/gram as raw material. This low cost alternative to rHSA can be scaled up easily. In this phase I SBIR proposal, we plan to develop a homozygous line and characterize the transgenic plants. At the same time, we will develop rHSA purification procedure and prepare rHSA from rice grain. Then we will conduct in vitro protein analysis to compare biochemical and biophysical characteristics between rHSA and native HSA. In phase II, we will produce a large amount of rice grain and purify sufficient quantity of rHSA for both preclinical and clinical trials with both model animals and human subjects. Our long term goal is to produce large quantities and high quality of rHSA at cost comparable to blood derived HSA for therapeutic applications.