Biosynthetic pathway deflection – a new cell line engineering approach
© Horsten et al; licensee BioMed Central Ltd. 2011
Published: 22 November 2011
With increasing information on genome, transcriptome and metabolome of commonly used production cell lines, engineering becomes an increasingly popular approach to achieve desired product attributes, growth behavior and nutrient consumption. Tools range from feeding intermediate metabolites, overexpression or deregulation of key enzymes of a pathway to knock-out and RNA silencing. While conceptionally simple, the latter approaches are either labor intensive or costly to apply at large scale.
Fucose targeted glycoengineering
The approach allows producing antibodies that are devoid of core fucose at Fc glycans of the CH2 domain . This modification provides higher flexibility to the Fc-region of IgG1 antibodies and enhances their binding to the FcγRIIIa receptor of NK cells - the dominating effector cells in antibody dependent cytotoxicity (ADCC). Consequently, the potency of antibodies directed against tumor or infected cells is substantially increased.
In contrast to other strategies the approach is easily applied to the starter cell line of choice and, moreover, allows modification of fully developed producer cell lines within weeks.
Simultaneous regulation of multiple cellular pathways
CDC42-mediated relative mAb-titer increase over native clone titers. The clones represent five different products.
Titers of Naïve mAb producing clones
Titers of cdc42-engineered mAb producing clones
Relative Fold Increase per modified clone
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