Methamphetamine is a highly addictive psychostimulant with tens of millions of abusers around the world, and currently there is no effective or approved medication for addiction to it. Monoclonal antibodies with a high affinity for methamphetamine have the potential to sequester the drug in the vascular compartment and reduce entry into the brain, acting as peripheral pharmacokinetic antagonists without inducing adverse effects on neurons. However, in order to maintain the antibodies at an effective level, repeated administration is required, which would be expensive and problematic for patient compliance. In this study, we intended to investigate whether using a recombinant adeno-associated virus-mediated gene transfer technique can be an effective approach to achieve long-term expression of anti-methamphetamine monoclonal antibodies in mouse models. We generated a recombinant adeno-associated virus vector encoding the heavy and light chains of an anti-methamphetamine monoclonal antibody, which were constructed in a single open reading frame and linked with a 2A self-processing sequence. In the context of virus-mediated gene transfer, expression of full-length and functional monoclonal antibodies was successfully demonstrated in vitro and in vivo. Further investigations on dose optimization, long-term expression, and protection from methamphetamine challenge in mouse models are ongoing.

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甲基苯丙胺滥用的治疗：一种基于抗体的免疫治疗方法

甲基苯丙胺是一种高度成瘾的精神兴奋剂，在全球有数千万的滥用者，目前还没有有效或批准的药物可用于成瘾。对甲基苯丙胺具有高亲和力的单克隆抗体有可能将药物隔离在血管隔室中并减少进入大脑，作为外周药代动力学拮抗剂而不会对神经元产生不良影响。然而，为了将抗体维持在有效水平，需要重复给药，这对于患者的依从性而言将是昂贵且成问题的。在这项研究中，我们打算研究使用重组腺相关病毒介导的基因转移技术是否可以成为在小鼠模型中实现抗甲基苯丙胺单克隆抗体长期表达的有效方法。我们生成了编码抗甲基苯丙胺单克隆抗体的重链和轻链的重组腺相关病毒载体，其构建在单个开放阅读框架中，并与 2A 自我加工序列相连。在病毒介导的基因转移的背景下，在体外和体内成功地证明了全长和功能性单克隆抗体的表达。正在对小鼠模型中的剂量优化、长期表达和对甲基苯丙胺攻击的保护进行进一步研究。我们生成了编码抗甲基苯丙胺单克隆抗体的重链和轻链的重组腺相关病毒载体，其构建在单个开放阅读框架中，并与 2A 自我加工序列相连。在病毒介导的基因转移的背景下，在体外和体内成功地证明了全长和功能性单克隆抗体的表达。正在对小鼠模型中的剂量优化、长期表达和对甲基苯丙胺攻击的保护进行进一步研究。我们生成了编码抗甲基苯丙胺单克隆抗体的重链和轻链的重组腺相关病毒载体，其构建在单个开放阅读框架中，并与 2A 自我加工序列相连。在病毒介导的基因转移的背景下，在体外和体内成功地证明了全长和功能性单克隆抗体的表达。正在对小鼠模型中的剂量优化、长期表达和对甲基苯丙胺攻击的保护进行进一步研究。在体外和体内成功地证明了全长和功能性单克隆抗体的表达。正在对小鼠模型中的剂量优化、长期表达和对甲基苯丙胺攻击的保护进行进一步研究。在体外和体内成功地证明了全长和功能性单克隆抗体的表达。正在对小鼠模型中的剂量优化、长期表达和对甲基苯丙胺攻击的保护进行进一步研究。