Many of the bestselling medicines are recombinant proteins produced by CHO cells with many more mammalian-cell-derived recombinant therapeutic proteins in development.
Progressive improvements in manufacturing technologies — from genetic vector engineering to process engineering — have substantially intensified production processes, enabled control of product molecular heterogeneity and importantly, reduced development time. A key issue for CHO cell utilisation is genome plasticity, rearrangement and instability that often result in the loss of the transgenes. We have discovered a number of robustly stable, highly-expressing genomic sites into which we have engineered a landing pad platform.
We have demonstrated efficient site-specific recombinase-mediated insertion of genetic constructs into the landing pad site on a CHO chromosome to enable the stable expression of proteins for an extended period of time:
Existing technology relies on the biologic expressing transgenes integrating randomly into the host chromosome which results in highly variable protein expression between transfectants. The advantages offered by the genomic locations identified enable the stable expression of proteins over many generations which is critical for replicable industrial protein production processes.
Edinburgh researchers have engineered CHO cell lines to stably produce high quantities of protein through the identification of novel hot spots to enable exogenous nucleic acid sequences to be targeted to these sites for stable protein expression.
Header image: Microscope image of cells with stable GFP expression at one of our newly defined genomic locations.