title: Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice.
abstract: 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.
authors.affiliation: Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.|Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yun-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Kuo-Jen
authors.initials: KJ
authors.lastname: Wu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Kuang-Lun
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Department of Electrical Engineering of I-Shou University, Kaohsiung, Taiwan.
authors.forename: Kun-Lieh
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ho-Min
authors.initials: HM
authors.lastname: Tsai
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Wei
authors.initials: W
authors.lastname: Hsieh
authors.affiliation: Department of Microbiology, Soochow University, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Lin
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D019969:Amphetamine-Related Disorders / Q000150:complications / Q000628:therapy*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D000229:Dependovirus / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006948:Hyperkinesis / Q000209:etiology / Q000628:therapy*; D007116:Immunization, Passive / Q000379:methods*; D008297:Male; D008694:Methamphetamine / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D057134:Antibodies, Neutralizing; D008694:Methamphetamine