Document Detail


Identification of Escherichia coli host cell for high plasmid stability and improved production of antihuman ovarian carcinoma x antihuman CD3 single-chain bispecific antibody.
MedLine Citation:
PMID:  17598107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To improve the plasmid stability during the production of antihuman ovarian carcinoma x antihuman CD3 single-chain bispecific antibody (AhOCxAhCD3), the Escherichia coli BL21(DE3) host cell was optimized serially. Firstly, an isogenic recombination-deficient (recA (-)) derivative of BL21(DE3), namely BLR(DE3), was used as host instead of BL21(DE3). Although the segregational plasmid stability was greatly improved, AhOCxAhCD3 yield was not improved due to the severe growth inhibition of plasmid-bearing BLR(DE3) cells and the competitive plasmid instability after induction. Secondly, a mutant BLR(DE3), namely BLRM(DE3), was screened by using LB agar plates plus ampicillin and isopropyl-beta-D: -thiogalactopyranoside. Using this new host, growth inhibition of recombinant cells after induction was eliminated, and plasmids could be stably maintained even after long-time induction in a nonselective medium. At last, about 1.2 g/l AhOCxAhCD3, which was about thrice as much as those of recombinant BL21(DE3) and BLR(DE3) strains, was yielded.
Authors:
Jing-Bo Zhao; Dong-Zhi Wei; Wang-Yu Tong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-28
Journal Detail:
Title:  Applied microbiology and biotechnology     Volume:  76     ISSN:  0175-7598     ISO Abbreviation:  Appl. Microbiol. Biotechnol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-29     Completed Date:  2007-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406612     Medline TA:  Appl Microbiol Biotechnol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  795-800     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Bispecific / biosynthesis*,  genetics,  immunology
Antigens, CD3 / genetics,  immunology*
Biotechnology / methods*
Escherichia coli / genetics
Female
Gene Deletion
Humans
Immunotherapy / methods
Ovarian Neoplasms / immunology*,  therapy
Plasmids / genetics,  immunology
Rec A Recombinases / genetics
Recombinant Proteins / biosynthesis,  genetics,  immunology
Chemical
Reg. No./Substance:
0/Antibodies, Bispecific; 0/Antigens, CD3; 0/Recombinant Proteins; EC 2.7.7.-/Rec A Recombinases

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