Daichang Yang, Jiquan Ou, Bo Shi, Jingni Shi, Yang He, Tingting Ning and Tingting Xie
Wuhan Institute of Biotechnology and Wuhan Healthgen Biotechnology Corp., Biolake, Wuhan, China
Human serum albumin (HSA) is a soluble, globular, and unglycosylated monomeric protein, which is widely used clinically to treat serious burn injuries, hemorrhagic shock, hypoproteinemia, fetal erythroblastosis, and ascites caused by cirrhosis of the liver. HAS is also used as an excipient for vaccines or therapeutic protein drugs and as a cell culture medium supplement in the production of vaccines and pharmaceuticals. Many other novel uses for HSA in biological applications have recently been explored, such as carrier of oxygen, nanodelivery of drugs, and fusion of peptides. The market demand for HSA is estimated at more than 800 tons per year worldwide. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. We developed an endosperm-specific expression platform for large scale the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 0.96 % of brown rice biomass. Physical and biochemical characterization of OsrHSA revealed it is equivalent to plasma-derived HSA (pHSA). The preclinical trial has been accomplished. The results demonstrated that the efficacy of hemorrhagic shock and ascites cirrhosis are equivalent to pHSA; no significant differences between pHSA and OsrHSA on maximum tolerated embryo-fetal developmental toxicity test (II stage), distribution and excretion in SD rats, acute toxicology and pharmacokinetics in both SD rate and M. Fascicularis, toxicology for central nervous system (CNS), long term toxicity tests in M. Fascicularis are observed. Our results provide evidence that OsrHSA is cost-effective and safe, which can replace of pHSA to satisfy an increasing worldwide demand for human serum albumin.
Keywords: OrsHSA, rice endosperm expression platform, preclinical trial, toxicity.