Li Yuanyuan, Kong Qingyao, Yue Jiping, Gou Xuewen, Xu Ming, Wu Xiaoyang
Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.
Nat Biomed Eng. 2019 Feb;3(2):105-113. doi: 10.1038/s41551-018-0293-z. Epub 2018 Sep 17.
Cocaine addiction is associated with compulsive drug-seeking, and exposure to the drug or to drug-associated cues leads to relapse, even after long periods of abstention. A variety of pharmacological targets and behavioral interventions have been explored to counteract cocaine addiction, but to date no market-approved medications for treating cocaine addiction or relapse exist, and effective interventions for acute emergencies resulting from cocaine overdose are lacking. We recently demonstrated that skin epidermal stem cells can be readily edited by using CRISPR (clustered regularly interspaced short palindromic repeats) and then transplanted back into the donor mice. Here, we show that the transplantation, into mice, of skin cells modified to express an enhanced form of butyrylcholinesterase, an enzyme that hydrolyzes cocaine, enables the long-term release of the enzyme and efficiently protects the mice from cocaine-seeking behavior and cocaine overdose. Cutaneous gene therapy through skin transplants that elicit drug elimination may offer a therapeutic option to address drug abuse.
可卡因成瘾与强迫性觅药行为相关，即使经过长时间戒断，接触该药物或与药物相关的线索也会导致复吸。人们已经探索了多种药理学靶点和行为干预措施来对抗可卡因成瘾，但迄今为止，尚无经市场批准用于治疗可卡因成瘾或复吸的药物，并且缺乏针对可卡因过量导致的急性紧急情况的有效干预措施。我们最近证明，使用CRISPR（成簇规律间隔短回文重复序列）可以轻松编辑皮肤表皮干细胞，然后将其移植回供体小鼠体内。在此，我们表明，将经过修饰以表达增强型丁酰胆碱酯酶（一种可水解可卡因的酶）的皮肤细胞移植到小鼠体内，能够使该酶长期释放，并有效保护小鼠免受觅药行为和可卡因过量的影响。通过引发药物消除的皮肤移植进行皮肤基因治疗可能为解决药物滥用问题提供一种治疗选择。
