Using targeted gene editing to disable a specific part of glutamine synthetase creates high-producing CHO cells for making antibodies

The exon 7-edited variant of the glutamine synthetase gene achieved higher titers and specific productivities in monoclonal antibody production compared to the standard CHOZN™ line.

• Variable performance was observed between two commercial CHO lines due to distinct intragenic GS deletions.
• Differential residual transcript levels suggest that the position of the premature termination codon (PTC) may influence cellular performance.
• Introducing PTCs into Glul coding exons revealed that the E7 variant resulted in complete GS ablation while maintaining high cell viability.
• In fed-batch production, the E7 variant outperformed the CHOZN™ line in terms of antibody titers and specific productivities.
• The location of the PTC is indicated as a crucial factor affecting GS knockout completeness and overall cellular phenotype.

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