A number of platforms exist for developing high specific productivity stable mammalian cell lines. The most commonly employed platform takes advantage of a single gene capable of rescuing a specific metabolic defect or auxotrophy in the parental cell line. Examples are the dihydrofolate reductase (dhfr)-deficient Chinese Hamster Ovary (CHO) cell line variants, and the glutamine synthetase (GS) NS0 (non-secreting null) murine myeloma line. The CHOLCelect system exploits another known auxotrophy of NS0 cells, one related to cholesterol biosynthesis. This auxotrophy has been mapped to a deficiency in expression from the 17beta-hydroxysteroid dehydrogenase type 7 gene (HSD17B7) locus in the NS0 genome. A vector expressing HSD17B7 rescues the cholesterol biosynthetic deficiency in transfected NS0, allowing cells to grow in cholesterol-free medium. Thus, a system was engineered that allows generation of stable NS0 lines using this novel selection method. This system has several advantages over the NS0-GS system: 1. Stable cell lines can be generated from the onset in chemically defined serum-free medium (CD-SFM); 2. Medium is supplemented with highly soluble glutamine, but not with cholesterol, which is commonly supplied in carbohydrate-coupled form to retain solubility; 3. Cell lines can be generated in approximately half the time of conventional methods, thus permitting a significant reduction in development timelines for leading candidate biologicals. We commonly generate clonal stable NS0 lines in our laboratory in ~60 days.
Product co-development partnerships
Zalgen Labs employs the CHOLCelect system to generate its leading candidate molecules requiring expression in mammalian systems. The system available for co-development of biologicals between Zalgen Labs and commercial, academic, and institutional entities.
The CHOLCelect NS0-based platform is also commercially available from Zalgen Labs.
To request additional information regarding contract cell line development and CHOLCelect licensing options contact us via the quick contact box.