Glycobiology World Congress

Biography

Biography: Jiahua Jay Xie

Abstract

Asialo-rhuEPO, a non-hematopoietic recombinant human erythropoietin (EPO) derivative lacking sialic acid, has been reported to display broad tissue-protective effects against damage triggered by ischemia/reperfusion, hypoxia or cytotoxic agents in the brain, the heart, the kidneys and the liver. However, attempts to translate its protective effects into clinical practice is hampered by unavailability of suitable expression system and its costly and limit production from expensive mammalian cell-made EPO (rhuEPOM) by enzymatic desialylation. It is known that plants can synthesize complex N-glycans similar to mammals, but lack sialylating capacity. In our lab, we generated stable transgenic tobacco lines co-expressing human EPO and β1,4-galactosyltransferase (GalT) genes to produce asialo-rhuEPO (asialo-rhuEPOP) lacking sialic acid, but bearing mammalian-type β1,4-galactose residues. We also developed an efficient purification system for isolating asialo-rhuEPOP from leaf tissues both at small scale (grams) and medium scale (kilograms). Purified asialo-rhuEPOP from transgenic tobacco leaves was found to have superior cytoprotective effect than rhuEPOM in protecting neuronal-like mouse neuroblastoma cells, murine HL-1 cardiomyocytes and pancreatic β-cells from staurosporine-induced cell death. These milestone studies have set the stage for the future investigations on its tissue-protective effects and action mechanisms in various animal models of tissue injury.