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Viral vector-mediated gene therapy for opioid use disorders
1Department of Anesthesiology, Perioperative Medicine & Pain Management, University of Miami Miller School of Medicine, Miami, FL, United States of America.
Abstract:
Chronic exposure to opioids typically results in adverse consequences. Opioid use disorder (OUD) is a disease of the CNS with behavioral, psychological, neurobiological, and medical manifestations. OUD induces a variety of changes of neurotransmitters/neuropeptides in the nervous system. Existing pharmacotherapy, such as opioid maintenance therapy (OMT) is the mainstay for the treatment of OUD, however, current opioid replacement therapy is far from effective for the majority of patients. Pharmacological therapy for OUD has been challenging for many reasons including debilitating side-effects. Therefore, developing an effective, non-pharmacological approach would be a critical advancement in improving and expanding treatment for OUD. Viral vector mediated gene therapy provides a potential new approach for treating opioid abused patients. Gene therapy can supply targeting gene products directly linked to the mechanisms of OUD to restore neurotransmitter and/or neuropeptides imbalance, and avoid the off-target effects of systemic administration of drugs. The most commonly used viral vectors in rodent studies of treatment of opioid-used disorder are based on recombinant adenovirus (AV), adeno-associated virus (AAV), lentiviral (LV) vectors, and herpes simplex virus (HSV) vectors. In this review, we will focus on the recent progress of viral vector mediated gene therapy in OUD, especially morphine tolerance and withdrawal.
Insights
Gene therapy offers a promising non-pharmacological treatment for opioid use disorder (OUD). Viral vectors deliver targeted gene products to correct neurochemical imbalances, addressing challenges with current opioid maintenance therapy (OMT).
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Opioid use disorder (OUD) is a complex CNS disease with limited treatment efficacy.
- Current pharmacotherapies like opioid maintenance therapy (OMT) have significant limitations and side effects.
- Developing novel, non-pharmacological treatments is crucial for improving OUD management.
Purpose of the Study:
- To review recent advancements in viral vector-mediated gene therapy for OUD.
- To highlight gene therapy's potential to restore neurotransmitter balance and mitigate OUD symptoms.
- To focus on gene therapy's application in addressing morphine tolerance and withdrawal.
Main Methods:
- Review of current literature on viral vector gene therapy for OUD in preclinical models.
- Focus on commonly used viral vectors: adenovirus (AV), adeno-associated virus (AAV), lentiviral (LV), and herpes simplex virus (HSV).
- Analysis of gene therapy's mechanism in targeting OUD's neurobiological underpinnings.
Main Results:
- Viral vector gene therapy demonstrates potential for targeted treatment of OUD.
- Gene therapy can restore neurotransmitter/neuropeptide balance, avoiding systemic drug side effects.
- Specific viral vectors show promise in preclinical models for OUD, including morphine tolerance and withdrawal.
Conclusions:
- Viral vector gene therapy presents a novel and potentially effective non-pharmacological strategy for OUD.
- This approach offers a way to directly address the neurobiological mechanisms of OUD.
- Further research into gene therapy holds promise for advancing OUD treatment options.
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