The production, characterisation and enhanced pharmacokinetics of scFv-albumin fusions expressed in Saccharomyces cerevisiae
The production, characterisation and enhanced pharmacokinetics of scFv-albumin fusions expressed in Saccharomyces cerevisiae
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DOI：
10.1016/j.pep.2010.05.009
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发表时间：
2010-10-01
影响因子：
1.6
通讯作者：
Sleep, Darrell
中科院分区：
文献类型：
--
作者：
Evans, Leslie;Hughes, Miranda;Sleep, Darrell
描述了用于产生与人白蛋白（在N-或C-末端或两者）遗传融合的单体scFv和scFv抗体片段的表达系统。基于最初开发用于生产重组人白蛋白（Recombumin（R））的酿酒酵母菌株，该系统将高水平的分泌产物递送到摇瓶和高细胞密度补料分批发酵的上清液中。对于每种scFv和scFv-白蛋白融合物，证明了与相应配体的特异性结合，并且药代动力学研究表明融合产物具有大大延长的循环半衰期。所描述的系统提供了一个有吸引力的替代其他微生物系统用于生产这种类型的产品。(C)2010年爱思唯尔公司版权所有© 2016
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,