Leveraging Gene Copy Number to Optimize Expression for Rapid, High-Titer Production of Complex Products in CHO Cells with GPEx® Lightening
Abstract: Biotherapeutics are becoming increasingly sophisticated, often requiring the coordinated expression of multiple genes, processing enzymes, and cofactors. This complexity poses significant challenges for cell line development and manufacturability. To address these challenges, we’ve engineered a novel cell line development platform capable of inserting over 100 transgene copies into predefined dock sites across the CHO genome. By placing each gene on a separate expression plasmid and adjusting the amount of each plasmid in the transfection mix, we can precisely and predictably control the integrated copy number, and thus expression, of each gene. In contrast to traditional methods, that utilize a small number of transgene copies and modulate expression by altering genetic elements (e.g. promoters, enhancers, introns), our approach enables simple and rapid screening of diverse expression levels for each gene in high-titer pools. By leveraging this technology, we achieve higher titer, improved product quality, robust manufacturing processes, and faster development timelines.