Chen Zhen, He Yang, Shi Bo, Yang Daichang
Engineering Research Center for Plant Biotechnology and Germplasm Utilization, Ministry of Education, Wuhan University, Wuhan 430072, China; State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Biochim Biophys Acta. 2013 Dec;1830(12):5515-25. doi: 10.1016/j.bbagen.2013.04.037. Epub 2013 May 3.
As the most abundant protein in the blood, human serum albumin (HSA) plays an important role in maintaining plasma oncotic pressure and fluid balance between the body's compartments. HSA is thus widely used in the clinic to treat diseases. However, the shortage of and safety issues arising from using plasma HSA (pHSA) underscore the importance of recombinant HSA (rHSA) as a promising substitute for pHSA.
Here, we review the production of rHSA, from expression to downstream processing, and highlight the scalability and cost-effectiveness of the two main expression platforms. We also discuss the biosafety of commercially available pharmaceutical rHSA with respect to impurities and contaminants, followed by an analysis of recent progress in preclinical and clinical trials. We emphasise the challenges of producing pharmaceutical-grade rHSA.
rHSA can be highly expressed in various hosts and seems to be identical to pHSA. rHSA generated from yeast appears to be as efficient and safe as pHSA in a series of preclinical and clinical trials, whereas rHSA from rice seeds exhibits great potential for more cost-effective production. Cost-effective products with no adverse effects will likely play a vital role in future human therapeutics.
Our understanding of pharmaceutical-grade rHSA production has improved with respect to expression hosts, biochemical properties, downstream processing, and the detection and removal of impurities. However, due to the large dosages required for clinical applications, the production of sufficient quantities of rHSA still presents challenges. This article is part of a Special Issue entitled Serum Albumin.
作为血液中含量最丰富的蛋白质，人血清白蛋白（HSA）在维持血浆渗透压和人体各腔室间的液体平衡方面发挥着重要作用。因此，HSA在临床上被广泛用于治疗疾病。然而，使用血浆HSA（pHSA）存在供应短缺和安全问题，这凸显了重组HSA（rHSA）作为pHSA有前景的替代品的重要性。
在此，我们综述了rHSA从表达至下游加工的生产过程，并强调了两种主要表达平台的可扩展性和成本效益。我们还讨论了市售药用rHSA在杂质和污染物方面的生物安全性，随后分析了临床前和临床试验的最新进展。我们强调了生产药用级rHSA的挑战。
rHSA可在多种宿主中高效表达，且似乎与pHSA相同。在一系列临床前和临床试验中，酵母来源的rHSA似乎与pHSA一样有效和安全，而水稻种子来源的rHSA在更具成本效益的生产方面具有巨大潜力。无不良影响的高性价比产品可能会在未来人类治疗中发挥至关重要的作用。
我们对药用级rHSA生产的理解在表达宿主、生化特性、下游加工以及杂质的检测和去除方面都有所提高。然而，由于临床应用所需剂量较大，生产足够数量的rHSA仍然面临挑战。本文是名为《血清白蛋白》的特刊的一部分。
