Mechanistic rigor refers to the depth and quality of experimental evidence supporting the biological mechanism underlying a scientific observation.

• 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

• Fluorescent cargo delivery without demonstrating biological activity
• No exploration of endosomal escape or intracellular trafficking
• Absence of pathway dissection or rescue studies

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.