Valproic acid enhances recombinant mRNA and protein levels in transiently transfected Chinese hamster ovary cells.
Valproic acid (VPA) is a small molecule that inhibits histone deacetylase activity. Here we report that VPA increases recombinant mRNA and protein levels in transiently transfected CHO DG44 cells. In the presence of VPA, transient recombinant antibody yields of up to 40 mg/L were achieved in simple batch cultures. The steady-state levels of the IgG light and heavy chain mRNAs were nearly 10 times higher than in the untreated control transfection even though the level of transfected plasmid DNA was the same in the presence or absence of VPA. The combination of VPA treatment and incubation of the transfected cells in mildly hypothermic conditions resulted in recombinant antibody yields of over 90 mg/L by 6 days post-transfection in batch cultures. The results demonstrated that the treatment of transfected CHO DG44 cells with VPA is a cost-effective strategy for enhancing transient gene expression by increasing the transgene mRNA levels.
Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Laboratory of Cellular Biotechnology, CH-1015 Lausanne, Switzerland.
Sarah
S
Wulhfard
Lucia
L
Baldi
David L
DL
Hacker
Florian
F
Wurm
D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000032:analysis / Q000235:genetics; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D014162:Transfection; D014635:Valproic Acid / Q000494:pharmacology*
D007147:Immunoglobulin Light Chains; D007142:Immunoglobulin gamma-Chains; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014635:Valproic Acid; D004247:DNA