Scientific Poster

Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Donec ac odio tempor orci dapibus ultrices in iaculis nunc. Vitae sapien pellentesque habitant morbi tristique senectus. 

1 min read

Whole Genome Sequencing to Survey Genetic Changes in Stable CHO Cell Lines

May 14, 2017

Chinese hamster ovary (CHO) cells represent the most frequently applied host cell system for industrial manufacturing of recombinant protein therapeutics. Generating and identifying high producing clones in a fast and efficient way such that they do not lose their expression capability over time has been a major focus of the industry.

Using cytogentic analysis combined with next-generation sequencing technology and proprietary bioinformatic tools called SUREscan, provide us with a unique ability to quickly analyze the whole genome of any generated cell line. Our data show that phenotypic changes in growth behavior and metabolism typically cuased by cellular stress such as adaptation to a different media are associated with a rise in single nucleotide polymorphisms (SNPs). However, karyotype analysis of a large number of research cell banks (RCBs) revealed our CHO lineage is chromosomally  stable indicating that the critical stages of a call line production platform do not induce chromosomalchanges. This contrasts with previous studies that have sown large chromosomal rearrangements in CHO cell lines.

View PDF

Keywords: research cell bank CHO Chinese hamster ovary next-generation sequencing SUREscan recombinant protein whole genome sequencing single nucleotide polymorphisms chromosomal rearrangements
1 min read

CHO Cell Library for the Selection of Improved Recombinant Therapeutic Protein Production Clones

May 29, 2013

In an effort to improve product yield of mammalian cell lines, we have previously demonstrated that our proprietary DNA elements, Selexis Genetic Elements (SGEs), increase the transcription of a given transgene1, thus boosting the overall expression of a therapeutic protein drug in mammalian cells. However, there are additional cellular bottlenecks, notably in the molecular machineries of the secretory pathways. Most importantly, mammalian cells have some limitations in their intrinsic capacity to manage high level of protein synthesis as well as folding recombinant proteins. These bottlenecks often lead to increased cellular stress and, therefore, low production rates. Our specific approach involves CHO cell line engineering. We constructed a CHO-M library based upon the CHO-M genome and transcriptome and using unique proprietary transposon vectors harboring SGE DNA elements to compensate for rate-limiting factors. This CHO-Mplus library displays a diversity of greater than 1×107 auxiliary proteins involved in secretory pathway machineries and cellular metabolism. We show that our CHO-Mplus library enabled the selection of a clonal cell line expressing 10 fold more product by comparison to standard approaches.

View PDF

Keywords: Chinese hamster ovary genome CHO Cell protein production clones cellular bottlenecks CHO-Mplus Library transcriptome