Recombinant human serum albumin for therapeutic use

描述（由申请人提供）：由于来自合并供体血液的分级分离的人血清白蛋白（HSA）的潜在疾病污染风险以及HSA在治疗应用中的需求增加，重组人血清白蛋白（rHSA）的生产作为血液来源的HSA的替代品已变得有吸引力。虽然在各种蛋白质表达系统中，特别是在酵母中，已经取得了重大进展，但rHSA生产的成本非常高。由于资金需求较大，rHSA的生产规模有限，将无法满足市场需求。Ventria Bioscience已经开发了一种专有的蛋白质表达系统-稻米可以以低于0.22 /kg的成本生产，因此来源于稻米的rHSA可以以<0.04美元/克作为原料生产。这种rHSA的低成本替代品可以很容易地扩大规模。在第一阶段SBIR的建议，我们计划开发一个纯合线和转基因植物的特点。同时，我们还将研究rHSA的纯化工艺，从大米中制备rHSA。然后，我们将进行体外蛋白质分析，比较生化和生物物理特性之间的rHSA和天然HSA。在第二阶段，我们将生产大量的米粒，并纯化足够数量的rHSA，用于模型动物和人类受试者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rHSA，其成本与血液来源的HSA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.