AI-Guided Gene Therapy Blueprint Offers Non-Addictive Pain Relief in Mice

The Nature study maps pain-circuit activity to build a brain-targeted approach that imitates morphine’s analgesia without activating reward pathways.

Overview

Researchers at the University of Pennsylvania, with collaborators at Carnegie Mellon and Stanford, report a CNS-targeted gene therapy based on more than six years of NIH-supported work.
Imaging of pain-tracking neurons combined with an AI-driven mouse behavioral platform produced a quantitative pain readout that guided therapy design.
The approach targets opioid-sensitive neurons in the cingulate cortex using a synthetic μ-opioid receptor promoter to drive inhibitory signaling as a circuit-specific pain “off switch.”
In mouse models, activation delivered durable pain relief that mirrored morphine’s benefits without altering normal sensation or triggering reward-related behavior.
The team is initiating next-phase translational studies toward eventual clinical testing, with human safety, delivery, dosing, and regulatory assessments still ahead for a therapy aimed at widespread chronic pain.