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Processes 2013, 1(3), 296-311; doi:10.3390/pr1030296
Review

CHO Quasispecies—Implications for Manufacturing Processes

Received: 30 July 2013; in revised form: 10 September 2013 / Accepted: 22 September 2013 / Published: 11 October 2013
(This article belongs to the Special Issue Feature Papers)
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Abstract: Chinese hamster ovary (CHO) cells are a source of multi-ton quantities of protein pharmaceuticals. They are, however, immortalized cells, characterized by a high degree of genetic and phenotypic diversity. As is known for any biological system, this diversity is enhanced by selective forces when laboratories (no sharing of gene pools) grow cells under (diverse) conditions that are practical and useful. CHO cells have been used in culture for more than 50 years, and various lines of cells are available and have been used in manufacturing. This article tries to represent, in a cursory way, the history of CHO cells, particularly the origin and subsequent fate of key cell lines. It is proposed that the name CHO represents many different cell types, based on their inherent genetic diversity and their dynamic rate of genetic change. The continuing remodeling of genomic structure in clonal or non-clonal cell populations, particularly due to the non-standardized culture conditions in hundreds of different labs renders CHO cells a typical case for “quasispecies”. This term was coined for families of related (genomic) sequences exposed to high mutation rate environments where a large fraction of offspring is expected to carry one or more mutations. The implications of the quasispecies concept for CHO cells used in protein manufacturing processes are significant. CHO genomics/transcriptomics may provide only limited insights when done on one or two “old” and poorly characterized CHO strains. In contrast, screening of clonal cell lines, derived from a well-defined starting material, possibly within a given academic or industrial environment, may reveal a more narrow diversity of phenotypes with respect to physiological/metabolic activities and, thus, allow more precise and reliable predictions of the potential of a clone for high-yielding manufacturing processes.
Keywords: Quasispecies; CHO; protein manufacturing; genome remodeling; clonal screening Quasispecies; CHO; protein manufacturing; genome remodeling; clonal screening
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wurm, F.M. CHO Quasispecies—Implications for Manufacturing Processes. Processes 2013, 1, 296-311.

AMA Style

Wurm FM. CHO Quasispecies—Implications for Manufacturing Processes. Processes. 2013; 1(3):296-311.

Chicago/Turabian Style

Wurm, Florian M. 2013. "CHO Quasispecies—Implications for Manufacturing Processes." Processes 1, no. 3: 296-311.

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