Bringing Biologically Relevant Cells to Life - iPSC Technology in Discovery and Safety Assessment
Type II diabetes and its associated co-morbidities are a growing global epidemic affecting an esimated 300 million patients worldwide. There currently is an abscence of therapeutic alternatives for halting or reversing disease progression. Furthermore, there is a lack of siutable human cellular models that recapitulate the biology of pancreatic beta-cells and which allow for drug screening activities at scale. AstraZeneca, in collaboration with the laboratory of Professor Douglas Melton (Harvard), are developing protocols to generate iPSC derived, functional, pancreatic beta-cells, at a scale comensurate with industry scale drug discovery. Data presented here demonstrates the succesful application of these protocols and shows the qualification of the generated cells in relation to their biological context. These cells are now being used in screening to generate novel chemical equity and identify new targets. In addition, data is presented that highlights the promise and power of combining precise genome editing (PGE) with iPSC technology to drive target validation, in a human context, with a precison and speed that has hitherto been unachievable. A specific case study is presented relating to Salt Inducible Kinase (SIK) target validation in chronic obstructive pulmonary disease. Here, PGE is applied to determine specific SIK isoform involvement in driving anti-inflamatory phenotypes in iPSC derived macrophages. This approach can be seen as a model for future combination of these two technologies in the target validation space.