Engineered caspases directly rewire mutant Ras to cell death

The study exploits two universal features of natural caspase regulation—proximity-induced subunit assembly and modular separation of substrate recruitment from catalysis—to engineer conditionally active effector caspases. These 'Raspases' reconstitute into functional complexes only when mutant Ras is present, thereby rewiring oncogenic Ras signaling to apoptosis. The design is intended to spare normal cells while eliminating Ras-mutant cancer cells. As a preprint, the findings have not yet been peer-reviewed, but they suggest a novel therapeutic strategy for cancers driven by Ras mutations, which are common in pancreatic, colorectal, and lung cancers.