| Literature DB >> 24911584 |
John S Y Goh1, Yingwei Liu2, Kah Fai Chan1, Corrine Wan1, Gavin Teo1, Peiqing Zhang1, Yuanxing Zhang2, Zhiwei Song1.
Abstract
Recombinant glycoprotein drugs require proper glycosylation for optimal therapeutic efficacy. Glycoprotein therapeutics are rapidly removed from circulation and have reduced efficacy if they are poorly sialylated. Ricinus communis agglutinin-I (RCA-I) was found highly toxic to wild-type CHO-K1 cells and all the mutants that survived RCA-I treatment contained a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. These mutants are named CHO-gmt4 cells. Interestingly, upon restoration of GnT I, the sialylation of a model glycoprotein, erythropoietin, produced in CHO-gmt4 cells was shown to be superior to that produced in wild-type CHO-K1 cells. This addendum summarizes the applicability of this cell line, from transient to stable expression of the recombinant protein, and from a lab scale to an industrial scale perfusion bioreactor. In addition, CHO-gmt4 cells can be used to produce glycoproteins with mannose-terminated N-glycans. Recombinant glucocerebrosidase produced by CHO-gmt4 cells will not require glycan remodeling and may be directly used to treat patients with Gaucher disease. CHO-gmt4 cells can also be used to produce other glycoprotein therapeutics which target cells expressing mannose receptors.Entities:
Keywords: CHO glycosylation mutants; CHO-gmt4; N-acetylglucosaminyltransferase I (GnT I); erythropoietin; mannose-terminated N-glycans; recombinant glycoproteins; sialylation
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Year: 2014 PMID： 24911584 PMCID： PMC4143398 DOI： 10.4161/bioe.29490
Source DB: PubMed Journal: Bioengineered ISSN： 2165-5979 Impact factor: 3.269