Research Projects

Recombinant proteins are essential for treating various diseases and require mammalian cells for commercial production. Chinese hamster ovary (CHO) cell lines are the most preferred for producing biotherapeutics and vaccine candidates due to their glycosylation. The increasing demand for these therapeutic proteins has led to the need to increase their productivity. The pandemic has also highlighted the need to shorten clone development timelines for rapid protein production. Productivity of secretory proteins requires a well-coordinated signaling network between metabolic pathways, including protein secretion. A model super-producer should have favorable modifications in many genes simultaneously to ensure high efficiency of all cellular machineries contributing to protein synthesis and secretion. To reduce the timeline for clone development, it is crucial to develop host cells with improved characteristics for producing any recombinant protein. Targeting multiple genes simultaneously is challenging in synthetic biology and determining the right set of genes to target. The proposed project aims to utilize evolutionary adaptation to develop novel parental cell lines from CHOK1 cells that have improved capacity for processing and secretion of glycosylated recombinant proteins. Using these host cells, rCHO clones producing the receptor binding domain of the spike protein from SARS-COV2 will be developed to compare different cell line development strategies. A systems-level understanding of these adapted rCHO cells will be developed using RNAseq analysis and targeted genome sequencing.

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