CHO Glycosylation Mutants as Potential Host Cells to Produce Therapeutic Proteins with Enhanced Efficacy

被引:21
|
作者
Zhang, Peiqing [1 ]
Chan, Kah Fai [1 ]
Haryadi, Ryan [1 ]
Bardor, Muriel [1 ]
Song, Zhiwei [1 ]
机构
[1] ASTAR, Bioproc Technol Inst, Singapore 138668, Singapore
来源
关键词
Biopharmaceutical; CHO; EPO; Glucocerebrosidase; Glycosylation mutant; IgG; CMP-SIALIC-ACID; DEPENDENT CELLULAR CYTOTOXICITY; ENZYME REPLACEMENT THERAPY; GDP-FUCOSE TRANSPORTER; ZINC-FINGER NUCLEASES; NUCLEOTIDE SUGAR TRANSPORTERS; MANNOSE 4,6-DEHYDRATASE GMD; RECOMBINANT GLUCOCEREBROSIDASE; BIOPHARMACEUTICAL BENCHMARKS; ANTIINFLAMMATORY ACTIVITY;
D O I
10.1007/10_2012_163
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
CHO glycosylation mutants, pioneered by Stanley and co-workers, have proven to be valuable tools in glycobiology and biopharmaceutical research. Here we aim to provide a summary of our efforts to isolate industrially applicable CHO glycosylation mutants, termed CHO-gmt cells, using cytotoxic lectins and zinc-finger nuclease technology. The genetic defects in the glycosylation machinery in these cells lead to the production of recombinant glycoproteins with consistent and unique glycan structures. In addition, these mutant cells can be easily adapted to serum-free medium in suspension cultures, the condition used by the biotech industry for large-scale production of recombinant therapeutics. In light of the critical impact of glycosylation on biopharmaceutical performances, namely, safety and efficacy, the CHO-gmt lines have enormous potential in producing glycoprotein therapeutics with optimal glycosylation profiles, thus, representing a panel of ideal host cell lines for producing recombinant biopharmaceuticals with improved safety profiles and enhanced efficacy.
引用
收藏
页码:63 / 87
页数:25
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