We have developed several approaches to create cell lines with improve
d characteristics in cell culture. In some cases it has been possible
to isolate natural variants with useful properties. Cholesterol indepe
ndent variants of the mouse NSO myeloma cell line were isolated by clo
ning in a selective medium. A glutamine independent variant of a hyrid
oma was isolated by continuous (chemostat) culture under glutamine lim
ited conditions in the presence of glutamate. Choline independent cell
s were isolated from a choline limited chemostat. In an alternative ap
proach to modifying cell behaviour, we have used recombinant DNA techn
iques to introduce the glutamine synthetase (GS) gene to a hybridoma.
This resulted in glutamine independence and increased productivity.