Probing The CHO Genome And Gene Function Using ZFNs

Zinc finger nucleases (ZFNs) have proven to be a powerful tool for modifying genes. In comparison to traditional techniques, such as adding chemical or radiation based mutagens that cause various random mutations, ZFNs can create very accurate, targeted changes to the genome in a much more rapid fashion. For quite some time, SAFC has been applying ZFNs to the development of CHO (Chinese hamster ovary) cells to improve their productivity and processing characteristics for biopharmaceutical manufacturing.

SAFC's CHOZN® cell lines have been designed to make creating production clones for biopharmaceuticals faster and simpler. Utilizing ZFN technology, customers have reported a time savings of up to eight weeks in their cell line development processes.

From a biopharmaceutical cell line perspective, the ability to modulate the activity of two genes in particular has been seen to be important. The first is the modification of the dihydrofolate reductase (DHFR) gene and subsequent elimination of this enzyme's activity. This modification is commonly used as a selection process for production cell line development. Traditional CHO DHFR null mutants were created using a combination of chemical and radiation based mutagenesis. Often, these cells lines were found to grow poorly in chemically defined media and have additional liabilities that make them less than ideal as a platform cell line. Using ZFNs has allowed accurate and precise gene deletion within the DHFR gene leading to cell lines with improved growth or production characteristics.