2. Genomic stability of the host cell line

It is well known that CHO cells change their chromosome composition at random and frequently. In part this is the source of their easy adaptation to different culture conditions and the possibility to find extraordinary high producers during screening, even though this is connected with considerable effort and the requirement to test a large number of cells. However, it also precludes optimisation of the host as these properties will again be lost in the next screening step and it also reduces the stability of producer cell lines. Thus manipulation of the host cell line to achieve a higher degree of genomic stability is a must, especially if targeted integration and a pre-optimised, platform adapted host cell line is used for cell line generation.

Approaches:

  • Evaluation of genes involved in maintenance of genomic stability, aging and DNA repair both on the level of gene expression and existing mutations
  • Identification of suitable target genes for engineering
  • Verification of increased genomic stability by chromosome analyses and FISH


Target: Cell line with uniform and stable chromosome content