Document Detail


Engineering mammalian cells in bioprocessing - current achievements and future perspectives.
MedLine Citation:
PMID:  20392202     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Over the past 20 years, we have seen significant improvements in product titres from 50 mg/l to 5-10 g/l, a more than 100-fold increase. The main methods that have been employed to achieve this increase in product titre have been through the manipulation of culture media and process control strategies, such as the optimization of fed-batch processes. An alternative means to increase productivity has been through the engineering of host cells by altering cellular processes. Recombinant DNA technology has been used to over-express or suppress specific genes to endow particular phenotypes. Cellular processes that have been altered in host cells include metabolism, cell cycle, protein secretion and apoptosis. Cell engineering has also been employed to improve post-translational modifications such as glycosylation. In this article, an overview of the main cell engineering strategies previously employed and the impact of these strategies are presented. Many of these strategies focus on engineering cell lines with more efficient carbon metabolism towards reducing waste metabolites, achieving a biphasic production system by engineering cell cycle control, increasing protein secretion by targeting specific endoplasmic reticulum stress chaperones, delaying cell death by targeting anti-apoptosis genes, and engineering glycosylation by enhancing recombinant protein sialylation and antibody glycosylation. Future perspectives for host cell engineering, and possible areas of research, are also discussed in this review.
Authors:
Yiping Lim; Niki S C Wong; Yih Yean Lee; Sebastian C Y Ku; Danny C F Wong; Miranda G S Yap
Publication Detail:
Type:  Journal Article; Review     Date:  2010-04-07
Journal Detail:
Title:  Biotechnology and applied biochemistry     Volume:  55     ISSN:  1470-8744     ISO Abbreviation:  Biotechnol. Appl. Biochem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-15     Completed Date:  2010-07-12     Revised Date:  2010-09-01    
Medline Journal Info:
Nlm Unique ID:  8609465     Medline TA:  Biotechnol Appl Biochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-89     Citation Subset:  IM    
Affiliation:
Department of Chemical Engineering and Chemical Technology, Imperial College London, London SW7 2AZ, UK. lim_yiping@bti.a-star.edu.sg
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Bioengineering / methods*,  trends
Cell Culture Techniques / methods*,  trends
Cell Cycle
Glycosylation
Humans
Mammals
Metabolomics
Recombinant Proteins / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Recombinant Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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