SAFC introduces CHOZN ZFN-modified CHO cell lines
To speed up the production of biopharmaceuticals
SAFC, the custom manufacturing group within US firm Sigma-Aldrich, has launched a product line of Zinc Finger Nuclease (ZFN)-modified Chinese hamster ovary (CHO) cell lines for use in the production of biopharmaceuticals.
SAFC says these CHOZN cell lines will enable biological drugs to reach the market faster and more cost-effectively.
The new line has been developed through CompoZr ZFN mediated gene editing of the dihydrofolate reductase (dhfr) locus in a CHO-K1 host. It allows process development scientists to use any common dhfr expression system for the selection and amplification in a fully traceable CHO-K1 background.
SAFC initially licensed ZFN technologies from Sangamo Biosciences in 2007, extending the licence to include commercial biopharmaceutical applications in 2009. This gave the firm tools to carry out gene editing in specific cell lines.
The firm started selling CompoZr ZFNs for individual knock-outs in October, but SAFC’s associate director of Cell Sciences and Development, Kevin Kayser, says not all customers have the time and expertise to use them to create their own cell lines.
SAFC has therefore created cell lines with some of the commonly requested knock-outs to sell to customers directly.
Kayser says the firm is also working on a glutamine synthetase (GS) knock-out CHO cell line (CHOZN GS), which will be launched towards the end of this year.
He claims this is the first time that this GS gene has been knocked out, even though blocking GS activity has previously been used in biomanufacturing processes.
‘By knocking out the GS gene, and hence the resulting enzymatic activity within the cell, CHOZN GS eliminates the need for the addition of that extra chemical within the development process, which is a good thing for risk mitigation, especially as this chemical has potential cytotoxic effects. It is also one less thing that has to be sourced from a vendor,’ he said.
Sangamo Biosciences itself is using ZFNs in cell therapy clinical trials, and Kayser says the regulatory burden is much higher for injecting modified cells into humans than it is for manufacturing within a ZFN-modified CHO line where the product is purified. One company is already carrying out clinical trials on a product that is made in these cell lines.
Pfizer has also decided to move forward with a cell line in which the GS gene has been disrupted using a ZFN as its primary manufacturing platform.
The next product launch from SAFC will be the CHOZN platform, which is scheduled to launch early next year.
‘This platform is intended to serve as a plug and play system for customers who seek an off-the -shelf cell line solution and will include an optimised CHO cell line, media, feeds and complete protocols for use in fed-batch production systems,’ Kayser said.