===== Mechanistic Rigor ===== **Mechanistic rigor** refers to the depth and quality of experimental evidence supporting the biological mechanism underlying a scientific observation. ==== Key Criteria ==== * Demonstrates causality, not just correlation * Includes mechanistic experiments (e.g., knockouts, inhibitors, pathway analysis) * Connects molecular events to phenotypic outcomes * Uses appropriate controls and model validation * Avoids overreliance on indirect or superficial readouts ==== Lack of Mechanistic Rigor ==== * Fluorescent cargo delivery without demonstrating biological activity * No exploration of endosomal escape or intracellular trafficking * Absence of pathway dissection or rescue studies ==== Example ==== A study showing Cas9-loaded EVs editing a gene and rescuing phenotype in a disease model demonstrates mechanistic rigor. A study showing only cargo uptake in cells does not.