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Academy Award-winning actors Octavia Spencer and Sean Penn awarded the Breakthrough Prize in Life Sciences to Stuart H. Orkin and Swee Lay Thein for research that transformed sickle cell disease and beta-thalassemia from incurable conditions to treatable ones through gene-editing therapy. Their work identified BCL11A as the master switch controlling fetal hemoglobin, leading directly to the development of Casgevy – the first CRISPR-based medicine approved for any disease.