Targeted gene modifications in drug discovery and development

In the present review, we discuss technologies and principles guiding the choice of cell-based assays. We show that a major trend is to expedite cell line development in cellular systems [stem cells, induced pluripotent stem cells (iPS), primary cells …] that may reflect the physiology and differentiation of cells in living organs. We discuss different expression technologies and propose that targeted gene integration is the best approach, applicable to all types of cells. We propose that targeted gene expression combined with the development of assays that approach the physiology of the human body, by creating better screening tools, may help to reduce failure and attrition rate at late stages of clinical development.