A Japanese research team has developed EV-SELEX, a novel DNA aptamer selection method that efficiently identifies drug candidates for G protein-coupled receptors (GPCRs). Using this approach, they discovered Dapt-μR, an aptamer that activates the opioid receptor and produces pain relief in mice. The technique could dramatically speed up drug development across neurology, pain, metabolism, and cancer.
Researchers at the University of Toyama, Japan, have unveiled a new drug discovery platform called EV-SELEX, designed to overcome a long-standing bottleneck in developing therapeutics for G protein-coupled receptors (GPCRs) — the most common drug targets in the human body. Traditional aptamer selection methods struggle with complex membrane proteins like GPCRs, but EV-SELEX sidesteps this by exploiting a natural cellular process: when a ligand activates a GPCR, the receptor gets internalized and packaged into extracellular vesicles (EVs), which are then released into the surrounding medium. Researchers can collect these EVs to isolate receptor-bound aptamers with far less interference from unrelated proteins.
Using EV-SELEX, the team identified Dapt-μR, a DNA aptamer that binds to and activates the μ-opioid receptor (MOR). In animal models, it produced analgesic effects after intrathecal administration — comparable to established opioid drugs — and its action was confirmed to be MOR-specific, as it was blocked by the antagonist naloxone.
Key Takeaways:
Why it matters: GPCRs are targeted by roughly one-third of all approved drugs, yet developing new candidates remains slow and difficult. EV-SELEX could give pharmaceutical companies a faster, more precise route to novel GPCR-targeting therapies — potentially accelerating treatments for some of medicine's most challenging conditions.
