Establishing genomic platforms for metabolic engineering in Chinese hamster ovary cells.

摘要

Chinese hamster ovary (CHO) cells are one of the most important host cell lines for production of recombinant therapeutic proteins; yet, the genetic and physiological properties that render them such capable protein producers and secretors are not well characterized. Research in other organisms has been revolutionized through the development of DNA sequence-based tools, like microarrays, high-throughput proteomics, Q-RT-PCR, and RNA interference. The lack of comparable genomic resources for the Chinese hamster has impeded similar work in CHO cells.; To facilitate biomolecular research in CHO cells, 16,136 unique CHO and Chinese hamster sequences have been isolated and used to develop both cDNA and Affymetrix microarrays. Comparative cross-species analysis and the projection of this sequence dataset into the context of model mammalian chromosomes, was used to develop a working scaffold for the Chinese hamster genome. This scaffold serves to develop biologically relevant connections, and provide access to the wealth of information available in public databases.; The next phase of process improvements in cell culture bioprocessing will likely be realized by metabolic engineering to harness the innate capabilities of host cell lines as producers of recombinant proteins. The information and tools generated through this work will contribute to the development of physiological insights and better direct bioprocess development in this important cell line.