Controllable Induction of Alpha-Synuclein Expression for Modeling Parkinson’s Disease When we model a disease, we introduce pathological changes through genetic manipulations. These changes produce a pathological phenotype, but frequently non-uniformly or too fast to assess possible compensatory mechanisms normally developed in patients. Parkinson’s disease is modeled in patient-derived cells cultured in 3D organoids. As in patients, an amyloid protein, a-syn, misfolds and accumulates in cells. However, months of culture are needed for pathological processes to naturally emerge, and methods that stimulate a-synuclein accumulation have two main problems: they don’t allow temporal control of α-syn load, and they don’t standardize the dose of a-syn per cell.