Approaches to optimizing animal cell culture process: substrate metabolism regulation and protein expression improvement.
Some high value proteins and vaccines for medical and veterinary applications by animal cell culture have an increasing market in China. In order to meet the demands of large-scale productions of proteins and vaccines, animal cell culture technology has been widely developed. In general, an animal cell culture process can be divided into two stages in a batch culture. In cell growth stage a high specific growth rate is expected to achieve a high cell density. In production stage a high specific production rate is stressed for the expression and secretion of qualified protein or replication of virus. It is always critical to maintain high cell viability in fed-batch and perfusion cultures. More concern has been focused on two points by the researchers in China. First, the cell metabolism of substrates is analyzed and the accumulation of toxic by-products is decreased through regulating cell metabolism in the culture process. Second, some important factors effecting protein expression are understood at the molecular level and the production ability of protein is improved. In pace with the rapid development of large-scale cell culture for the production of vaccines, antibodies and other recombinant proteins in China, the medium design and process optimization based on cell metabolism regulation and protein expression improvement will play an important role. The chapter outlines the main advances in metabolic regulation of cell and expression improvement of protein in animal cell culture in recent years.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China, yxzhang@ecust.edu.cn.
Yuanxing
Y
Zhang
D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods / Q000592:standards*; D019149:Bioreactors; D016466:CHO Cells; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D015870:Gene Expression; D007700:Kinetics; D010477:Perfusion; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D003470:Culture Media; D011994:Recombinant Proteins