Genome-edited Skin Transplants Offer a Safe and Enduring Gene Therapy Approach for Treating Drug Addiction John Luu
Canonical treatments of cocaine dependence are primarily behavioural therapy-based as there are no approved drugs or gene-based therapies for treatment (Fischer et al. 2015). Human butyrylcholinesterase (hBChE) has been engineered for extremely high specificity and catalytic potential for hydrolysis of cocaine (Zheng et al. 2014), but prior delivery strategies using fusion proteins and viral vectors have produced insubstantial results or are prone to high expenses and risk for therapeutic application (Gilgun-Sherki et al. 2016; Naldini 2015). Li and colleagues (2019) demonstrate the viability of editing epidermal stem cells for expression of engineered hBChE and grafting edited tissues into mice for protection against cocaine-induced toxicity and behaviour. Mice with hBChE-releasing skin grafts exhibited protection against cocaine overdose as well as significant reductions in cocaine seeking, hyperactivity, and relapse. The results support a powerful gene therapy approach for expression of therapeutic proteins that circumvents the primary obstacle of the hBChE enzyme’s short half-life (Brimijoin 2011) by enabling continued expression long-term. However, the authors did not address the impact on cocaine relapse induced by environmental cues—powerful conditioned stimuli primarily responsible for chronic relapse behaviour (Lee, Milton, and Everitt 2006); the authors may employ a conflict model of cue-induced relapse to test this (Katzir et al. 2007).
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