Document Detail

Valproic acid: a viable alternative to sodium butyrate for enhancing protein expression in mammalian cell cultures.
MedLine Citation:
PMID:  18454496     Owner:  NLM     Status:  MEDLINE    
Various DNA methyl transferase inhibitors (iDNMTs) and histone deacetylase inhibitors (iHDACs) were screened for their ability to enhance transient gene expression (TGE) in Human Embryonic Kidney 293-EBNA (HEK293E) cells. The effects in HEK293E cells were compared to those in Chinese Hamster Ovary DG44 (CHO-DG44) cells. The iDNMTs and iHDACs were chosen based on their different cellular activities and mechanisms of action. For each inhibitor tested, the optimum concentration was determined for both cell lines, and these conditions were used to evaluate the effect of each compound using a recombinant monoclonal antibody as a reporter protein. All the iHDACs increased transient antibody yield at least 4-fold in HEK293E and at least 1.5-fold in CHO-DG44. By comparison, the iDNMTs increased antibody yields by a maximum of approximately 2-fold. Pairwise combinations of iDNMTs and iHDACs had a linearly additive effect on TGE in CHO-DG44 but not in HEK293E. With valproic acid (VPA), volumetric and specific productivities of 200 mg/L and 20 pg/cell/day, respectively, were achieved in HEK293E cells with a 10-day process. As VPA is both FDA-approved and 5-fold less expensive than sodium butyrate (NaBut), we recommend it as a cost-effective alternative to this widely used enhancer of recombinant protein production from mammalian cells.
Gaurav Backliwal; Markus Hildinger; Ivan Kuettel; Fanny Delegrange; David L Hacker; Florian M Wurm
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Biotechnology and bioengineering     Volume:  101     ISSN:  1097-0290     ISO Abbreviation:  Biotechnol. Bioeng.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502021     Medline TA:  Biotechnol Bioeng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-9     Citation Subset:  IM    
Laboratory of Cellular Biotechnology, Institute of Bioengineering, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
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MeSH Terms
Antibodies, Monoclonal / biosynthesis*
Butyrates / administration & dosage*
Cell Line
Dose-Response Relationship, Drug
Gene Expression / drug effects,  physiology
Kidney / drug effects,  metabolism*
Protein Engineering / methods*
Valproic Acid / administration & dosage*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Butyrates; 99-66-1/Valproic Acid

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

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