Abstract
Erythropoietin is a major regulator of erythropoiesis which maintains the body’s red blood cell mass and tissue oxygenation at an optimum level. Recombinant human erythropoietin (rhEPO), which is a widely used therapeutic agent for the treatment of anemia and which represents one of the largest biopharmaceuticals markets, is produced from recombinant Chinese hamster ovary cells. rhEPO is a glycoprotein with complex glycan structure, which is responsible for its therapeutic efficacy, including the in vivo activity and half-life. In order to obtain an optimal and consistent glycoform profile of rhEPO and concurrently maintain a high production yield, various approaches in drug development and cell culture technology have been attempted. Recent advances in rhEPO production are classified into three types: the development of improved rhEPO molecules by protein engineering; improvement of production host cells by genetic engineering; and culture condition optimization by fine control of the production mode/system, process parameters, and culture media. In this review, we focus on rhEPO production strategies as they have progressed thus far. Furthermore, the current status of the market and outlook on rhEPO and its derivatives are discussed.
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This research was supported in part by the World Class University program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST, R31-2008-000-10071-0), the Converging Research Center Program through the NRF funded by the MEST (2009-0082276), and a grant from the Intelligent Synthetic Biology Center of Global Frontier Project funded by the MEST (2011-0031962), Republic of Korea.
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Lee, J.S., Ha, T.K., Lee, S.J. et al. Current state and perspectives on erythropoietin production. Appl Microbiol Biotechnol 95, 1405–1416 (2012). https://doi.org/10.1007/s00253-012-4291-x
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DOI: https://doi.org/10.1007/s00253-012-4291-x