Systematic identification of genomic hotspots for high-yield protein production in CHO cells.

Abstract in brief

• The study developed a systematic framework that uses multiomics data, including RNA sequencing and whole genome sequencing, to identify specific genomic hotspots in CHO cells for high-yield protein production, overcoming the variability seen with traditional random transgene integration.
• Out of 20 candidate loci, five top-performing hotspots were validated using CRISPR-Cas9 with Recombinasemediated cassette exchange (RMCE), achieving 22 to 150 times higher productivity compared to previous control sites for producing therapeutic proteins like enzymes and monoclonal antibodies.
• This innovative approach improves the stability, efficiency, and productivity of cell line development, significantly advancing biopharmaceutical manufacturing and enabling more reliable and high-yield production of therapeutic proteins.