Cellectis bioresearch, a specialist in genome customization and a subsidiary of Cellectis (Alternext: ALCLS), today announced the publication of a scientific study describing a novel method, based on meganuclease-driven targeted integration, for the generation of stable cell lines compatible with high throughput screening (HTS). The study demonstrated Cellectis bioresearch's technology to be faster, more reliable and efficient in deriving cell-based assays for HTS studies than classical methods. The study has been published online by Journal of Biomolecular Screening http://jbx.sagepub.com/cgi/content/abstract/1087057110375115v1.
The development of cell-based assays for HTS approaches is important to screen molecules on pharmaceutical targets and often requires the generation of stable cell lines. However, these cell lines are essentially created by random integration of a gene of interest (GOI) with no control over the level and stability of gene expression. In this study, scientists from the Servier Research institute used Cellectis bioresearch's cellular Genome Positioning System, or cGPS®, in CHO-K1 cells, to accomplish targeted integration of different GOIs. Five different GOIs representing 3 major drug target classes were stably integrated at the same locus in cGPS® CHO-K1 cells. Characterization of the targeted clones revealed that the cGPS® CHO-K1 system was more rapid (2-week protocol), efficient (all selected clones expressed the GOI), reproducible (GOI expression level variation of 12% maximum), and stable over time (no change in GOI expression after 23 weeks of culture) than classical random integration.
"Achieving a physiological level of expression compatible with the relevant functional assay is important in testing pharmaceutical targets", explained Jean Boutin, Director of the Molecular and Cellular Pharmacology Division of the SERVIER Research Institute. "We found that proteins expressed in the cGPS® CHO-K1 cells are biologically active and have enzymatic constants, localization and function close to the published values of their wild-type endogenous counterparts. This fast and robust method opens the door for creating large collections of cell lines expressing therapeutically relevant GOIs, enhancing the productivity of HTS".