Industry perspective on Chinese hamster ovary cell ‘omics’

The biopharmaceutical sector has become a significant segment of pharmaceutical industry. More than 200 biopharmaceutical products have reached market approval and more than 350 additional products are currently in clinical trials [1]. Chinese hamster ovary (CHO) cells are the main host for production of recombinant therapeutic proteins. The 2011 CHO-produced biopharmaceutical sales were nearly US$60 billion [2]. Approximately 45% of new products approved in the period from 2006 to 2010 produced in CHO cells and seven out of ten of the world’s top-selling biopharmaceutical drugs are expressed in CHO cells [1]. Despite some progress in improving therapeutic protein productivity, the cellular machinery of CHO cells is still not well understood and consequently good knowledge of recombinant protein production is missing. Therefore, functional genomics to better understand and improve productivity of CHO cell lines in pharmaceutical and biotech industry is getting more and more relevant. This includes applied genomic screening as well as cell line engineering tools. Thanks to recent advances in decoding the CHO cell genome and transcriptome [3–6] novel cell line engineering technologies as gene knockout (e.g., zinc finger nucleases [ZFNs], transcription activator-like effector nucleases [TALENs], clustered regularly interspaced short palindromic repeats [CRISPRs]), RNA interference (e.g., si/shRNA) as well as overexpression or introduction of new genes can now be applied to modify CHO cell lines. The expectation is that the now available Chinese hamster genomic information will lead to better understanding of the expression of recombinant proteins in CHO cells. This includes the utilization of genomics/ transcriptomic tools (e.g., next-generation sequencing [NGS], expression/comparative genomics microarray techniques), proteomic tools (e.g., mass spectrometry [MS]), as well as metabolomic techniques (e.g., nuclear magnetic resonance spectroscopy).