Many drug screens are based on targets that are considered to be relevant to the disease mechanisms. However, the low success rates of compounds originating from target-based screening have led to greater interest in phenotypic screening118. This revival in phenotypic screening has been aided by the discovery of iPSCs for numerous reasons, including the scalability of iPSC production, which facilitates assay development, and their pluripotency, which allows differentiation into multiple disease-relevant cell types (especially those that are otherwise hard to access, such as neurons)119. Patient-derived iPSC models make it possible to recapitulate disease phenotypes and pathologies in a culture dish. Cells differentiated from patient-derived iPSCs could present molecular and cellular phenotypes. Whether the phenotype that is selected as readout for drug screen is truly relevant to the disease can be confirmed by gene editing approach if the gene responsible for disease phenotypes is known, and can be further validated in patient samples and/or animal models120. In addition to phenotypic screening, iPSCs can also be used for target-based screening. Using human iPSC models, many drug screens have been conducted and potential drug candidates have been identified using either phenotypic or target-based screening.
