Human serum albumin from recombinant DNA technology: challenges and strategies

Background: 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.

Scope of review: 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.

Major conclusions: 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.

General significance: 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.