The production, characterisation and enhanced pharmacokinetics of scFv-albumin fusions expressed in Saccharomyces cerevisiae

被引：28

作者：

Evans, Leslie ^{[1
]}

Hughes, Miranda ^{[1
]}

Waters, Joanne ^{[1
]}

Cameron, Jason ^{[1
]}

Dodsworth, Neil ^{[1
]}

Tooth, David ^{[1
]}

Greenfield, Anthony ^{[1
]}

Sleep, Darrell ^{[1
]}

机构：

[1] Novozymes Biopharma UK Ltd, Castle Court, Nottingham NG7 1FD, England

来源：

PROTEIN EXPRESSION AND PURIFICATION | 2010年 / 73卷 / 02期

关键词：

Heterologous protein expression; scFv; scFv-albumin fusions; Albumin fusions; Saccharomyces cerevisiae; RECOMBINANT HUMAN ALBUMIN; HUMAN SERUM-ALBUMIN; UNFOLDED-PROTEIN RESPONSE; CHAIN ANTIBODY FRAGMENTS; YEAST PICHIA-PASTORIS; HETEROLOGOUS PROTEINS; ESCHERICHIA-COLI; GENE; STRAINS; TRANSFORMATION;

D O I：

10.1016/j.pep.2010.05.009

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

An expression system is described for the production of monomeric scFvs and scFv antibody fragments genetically fused to human albumin (at either the N- or C-terminus or both). Based upon strains of Saccharomyces cerevisiae originally developed for the production of a recombinant human albumin (Recombumin (R)) this system has delivered high levels of secreted product into the supernatant of shake flask and high cell density fed-batch fermentations. Specific binding to the corresponding ligand was demonstrated for each of the scFvs and scFv-albumin fusions and pharmacokinetic studies showed that the fusion products had greatly extended circulatory half-lives. The system described provides an attractive alternative to other microbial systems for the manufacture of this type of product. (C) 2010 Elsevier Inc. All rights reserved,

引用

页码：113 / 124

页数：12

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