Current oral formulations of donepezil, the primary acetylcholinesterase inhibitor for AD treatment, suffer from significant limitations, including the requirement for high systemic doses to achieve therapeutic brain concentrations, extensive first-pass hepatic metabolism, and dose-limiting peripheral side effects such as nausea, vomiting, and gastrointestinal bleeding that compromise patient compliance and quality of life4. The gene discussed is ACHE; the disease is Alzheimer disease.