Scalable Generation of Liver and Brain Organoids Derived from Human iPS Cells.

(Fast-Track and Direct to Phase II proposals will not be accepted. Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning.) Number of anticipated awards: 1 to 3 Budget (total costs, per award): Phase I: $325,000 for 9-12 months; Phase II: $2,000,000 for 2 years It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded. Summary: Disease modeling using 2D cells and 3D organoids derived from human induced pluripotent (iPS) cells is a fast-growing area in drug development and research. iPS cells reprogrammed from patient cells, such as dermal fibroblasts or peripheral blood mononuclear cells, can be differentiated into disease relevant 3D organoids. These disease relevant organoids could be used as in vitro disease models to study disease pathophysiology, evaluate drug candidate efficacy/toxicity, and conduct multi-omics analysis to identify new targets for drug discovery. This approach is especially useful for rare disease drug development, which often lacks animal models that represent human disease well. However, a major bottleneck to this approach is that current methods for generating organoids from iPS cells are labor-intensive, costly, and lack reproducibility. Human iPSC derived organoids are not commercially available as off the shelf products. Thus, development of a scalable method for generation of liver and brain organoids with reduced cost, and high quality and reproducibility is an unmet need