Stability of protein production from recombinant mammalian cells.

作者: Louise M. Barnes , Catherine M. Bentley , Alan J. Dickson

DOI: 10.1002/BIT.10517

关键词: CellProtein biosynthesisGene expressionChinese hamster ovary cellSecretionCell cultureGeneticsBiologyRecombinant DNACell biologyRegulation of gene expression

摘要: One of the most important criteria for successful generation a therapeutic protein from recombinant cell is to obtain line that maintains stability production. If this not achieved it can generate problems process yields, effective use time and money, regulatory approval products. However, selection sustains production over required period may be difficult achieve during development protein. There are several studies in literature have reported on instability lines. The causes varied and, many cases, exact molecular mechanisms unknown. proteins by cells modulated events at levels ranging transcription, posttranscriptional processing, translation, posttranslational secretion. potential regulation or all these stages. In study we review published information three industrially lines: hybridoma, Chinese hamster ovary (CHO), nonsecreting (NS0) myeloma We highlight likely loci which engendered indicate other areas affect mammalian cells. also outline approaches could help overcome associated with unpredictable expression maximized production, consequences might

参考文章(141)
Agnes Yeivin, Aharon Razin, Gene methylation patterns and expression Experientia. Supplementum. ,vol. 64, pp. 523- 568 ,(1993) , 10.1007/978-3-0348-9118-9_24
A Csordas, On the biological role of histone acetylation. Biochemical Journal. ,vol. 265, pp. 23- 38 ,(1990) , 10.1042/BJ2650023
N.H. Cossons, P.M. Hayter, M.F. Tuite, N. Jenkins, STABILITY OF AMPLIFIED DNA IN CHINESE HAMSTER OVARY CELLS Production of Biologicals from Animal Cells in Culture. pp. 309- 315 ,(1991) , 10.1016/B978-0-7506-1103-9.50063-9
T. Riedl, J-M. Egly, Phosphorylation in transcription: the CTD and more. Gene Expression. ,vol. 9, pp. 3- 13 ,(2001) , 10.3727/000000001783992704
Marilyn Kozak, A short leader sequence impairs the fidelity of initiation by eukaryotic ribosomes. Gene Expression. ,vol. 1, pp. 111- ,(1991)
M.S. Sinacore, S. Brodeur, S. Brennan, M. Fallon, S.R. Adamson, D. Cohen, Population analysis of a recombinant Chinese hamster ovary cell line expressing recombinant human protein cultured in the presence and absence of methotrexate selective pressure Animal Cell TechnologyProducts of Today, Prospects for Tomorrow. pp. 63- 68 ,(1994) , 10.1016/B978-0-7506-1845-8.50015-6
E.B. Lewis, The phenomenon of position effect. Advances in Genetics. ,vol. 3, pp. 73- 115 ,(1950) , 10.1016/S0065-2660(08)60083-8