Targeted, Exosome-Mediated Delivery of Opioid Receptor siRNA for Treatment of Morphine Addiction; Results Suggest “Brand New Strategy to Treat Drug Relapse and Diseases of the Central Nervous System”

Scientists at the Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology at Nanjing University in China have shown that exosomes modified to express the neuron-specific rabies viral glycoprotein (RVG) peptide on their membrane surface can be used to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. In an open-access article published online today (December 3, 2015) in Scientific Reports, the researchers described results demonstrating that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in these exosomes. The modified exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain, the scientists said. Functionally, the siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. The new article is titled “Targeted Exosome-Mediated Delivery of Opioid Receptor Mu siRNA for the Treatment of Morphine Relapse.” As background, the researchers said that MOR is a major target of opioid drugs and appears to play critical roles in mediating the major effects of these drugs, including analgesia, tolerance, abuse, dependence, and respiratory depression. It has been reported, the authors said, that the rewarding effect of morphine, mediated by MOR, is abolished in MOR-deficient mice and that a MOR antagonist diminished the consequences of an initial opioid drug relapse. Therefore, the researchers selected the MOR as a target for the treatment of drug addiction.
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