Opioids and opiates top the list of illicit drugs and cause the most burden of disease and drug-related deaths worldwide. The goal of this project is to develop a strategy to treat opioid addiction. We prepared exosomes (nano-sized vesicles secreted by endogenous cells) from cell factory that was engineered to express a rabies viral glycoprotein peptide (specifically recognize and target neuronal cells) on the exosomal membrane surface. By filling the exosomes with siRNA of the mu opioid receptor (MOR, a primary target for opioids) and injecting the exosomes into mouse bloodstream, we detected efficient passage of the siRNA through blood-brain barrier and specific accumulation of the siRNA in mouse brain. Consequently, siRNA-loaded exosomes significantly reduced MOR mRNA and protein levels in mice. To show the therapeutic potential, siRNA-loaded exosomes strongly restrained morphine-induced conditioned place preference in mice. This project may open up new avenues for future treatment of drug addiction.
