Cell Culture & Upstream Processing
How to Measure and Harness CHO Cell Genetic/Functional Instability for Improved Cell Factory Performance
The adaptability and utility of CHO cell factories derives from exploitation of their acquired genetic/functional hyper-variation using high-throughput functional screening and selection processes which enable industry to identify, isolate and maintain cell lineages with unusual and desirable manufacturing properties. However, the propensity of clonally derived cell populations to unpredictably change their functional performance by progressive genetic drift during subculture is also a significant problem. Clonal variation is both a blessing and a curse. How can we maximize benefit from clonal variation whilst limiting its deleterious consequences – minimizing resource expenditure on stability testing? For example, our data reveal that for the vast majority of isolated CHO subclonal populations, metabolic phenotype and culture performance drift markedly over extended subculture, with only a small proportion of subclones exhibiting both high culture performance and functional stability. New methods to both unlock the synthetic potential of CHO cells and ensure these remain stably inherited are required. In this presentation I will discuss new methodologies to (i) create functionally superior “biomass intensive” clonal variants through directed evolution and (ii) measure and predict clone-specific functional stability using rapid, multiparallel chemical stress fingerprinting.