Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice
Autor: | Mao-Liang Chen, Yun-Hsiang Chen, Kuang-Lun Wu, Kuo-Jen Wu, Chun-Ming Lin, Wei Hsieh, Ho-Min Tsai, Yi-Wei Chen, Kun-Lieh Wu, Yun Wang |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male medicine.drug_class viruses Amphetamine-Related Disorders Pharmacology Hyperkinesis medicine.disease_cause Monoclonal antibody Virus Article Viral vector Methamphetamine 03 medical and health sciences chemistry.chemical_compound Mice medicine Animals Humans Adeno-associated virus Mice Inbred ICR Multidisciplinary biology business.industry Immunization Passive Meth Dependovirus Antibodies Neutralizing 030104 developmental biology HEK293 Cells chemistry biology.protein Systemic administration Antibody business medicine.drug |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep46301 |
Popis: | Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse. |
Databáze: | OpenAIRE |
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