Current cell-based screens are poor models of human biology

Current cell assays for in vitro screening are based on genetically modified cell lines which are crude models of human biology. Typically, these assays have used immortalised cell lines derived from CHO or HEK293 cells engineered to express a discrete molecular target, the functionality of which is assayed using cell responses that are readily detected and quantified using automated fluid dispensing and detection systems.

Although the use of immortalised cell lines has yielded success, there are a number of recognised disadvantages including many differences in the physiology between these cells and human “normal” tissue.

To take account of these differences companies employ a two-stage screening process using primary human cells derived from tissue banks to refine the selection of identified lead compounds produced from cell-based assays. In addition to their use in screening drugs for initial “hits” against the disease target, cell-based assays are also used in the later screening of selected lead candidates for toxicity.

These systems typically use immortalized human cell lines and animal cell lines with the same inherent disadvantages described above. Animal models can be poor predictors of human liver or cardiac toxicity and moreover, the reaction to drugs can vary in sub-populations; this cannot be modelled easily with current assays.