Recombinant protein productivity in Chinese hamster ovary (CHO) cells often decreases over time during long-term cultures. This production instability is a longstanding problem in biopharmaceutical manufacturing processes. The gradual loss of recombinant protein expression can be associated with reduced transgene copy number due to CHO cells’ inherent genome instability. We have previously suggested that the DNA double-strand break (DSB) repair system in CHO may be deficient, leading to both genome and production instabilities. Therefore, increasing DSB repair may provide a method to improve production stability.<br/> <br/>In this study, we investigated the impact of improved DSB repair on protein production. Specifically, four production cell lines were established, each stably expressing a heterologous gene that was previously found to enhance DSB repair in CHO cells. A number of stable production clones were cultured over three months without methotrexate (MTX) selection. Growth rates and recombinant protein productivity were measured at initial, early, middle and late stages of the long-term culture. Growth and productivity changes and their correlation with the expression level of heterologous genes will be discussed.<br/>

Improved DNA double-strand break repair may reduce production loss in Chinese hamster ovary cells

255th National Meeting (2018)

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