The production of recombinant human erythropoietin.
Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.
Central Laboratories for Key Technology, Kirin Brewery Co. Ltd., Kanagawa, Japan.
N
N
Inoue
M
M
Takeuchi
H
H
Ohashi
T
T
Suzuki
D000595:Amino Acid Sequence; D000740:Anemia / Q000209:etiology / Q000628:therapy; D000818:Animals; D001483:Base Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular / Q000379:methods; D004921:Erythropoietin / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000627:therapeutic use; D005091:Exons; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009844:Oligosaccharides / Q000737:chemistry; D011994:Recombinant Proteins; D014162:Transfection / Q000379:methods
D015345:Oligonucleotide Probes; D009844:Oligosaccharides; D011994:Recombinant Proteins; D004921:Erythropoietin