Necessity refers to the justified need for a scientific or translational approach based on its potential to solve an unmet problem, address a clinical limitation, or improve upon existing strategies.

• Addresses an unmet clinical or biological need
• Provides clear improvement over current methods
• Demonstrates potential for real-world application
• Avoids redundancy or unjustified complexity

A delivery system that enables CRISPR gene editing in glioblastoma with fewer side effects than viral vectors meets the criterion of necessity. An overengineered fluorescent EV platform without therapeutic purpose does not.