Treatment of chronic pain by designer cells controlled by spearmint aromatherapy. (February 2018)

• Record Type: Journal Article
• Authors: Wang, Hui; Xie, Mingqi; Charpin-El Hamri, Ghislaine; Ye, Haifeng; Fussenegger, Martin
• Is Part Of: Nature biomedical engineering. Volume 2:Number 2(2018)
• Page Start: 114
• Page End: 123
• Publication Date: 2018-02
• Subjects: Biomedical engineering -- Periodicals; 610.2805
• DOI: 10.1038/s41551-018-0192-3
• Languages: English
• ISSNs: 2157-846X

Abstract

Abstract Current treatment options for chronic pain are often associated with dose-limiting toxicities, or lead to drug tolerance or addiction. Here, we describe a pain management strategy, based on cell-engineering principles and inspired by synthetic biology, consisting of microencapsulated human designer cells that produce huwentoxin-IV (a safe and potent analgesic peptide that selectively inhibits the pain-triggering voltage-gated sodium channel NaV 1.7) in response to volatile spearmint aroma and in a dose-dependent manner. Spearmint sensitivity was achieved by ectopic expression of the R-carvone-responsive olfactory receptor OR1A1 rewired via an artificial G-protein deflector to induce the expression of a secretion-engineered and stabilized huwentoxin-IV variant. In a model of chronic inflammatory and neuropathic pain, mice bearing the designer cells showed reduced pain-associated behaviour on oral intake or inhalation-based intake of spearmint essential oil, and absence of cardiovascular, immunogenic and behavioural side effects. Our proof-of-principle findings indicate that therapies based on engineered cells can achieve robust, tunable and on-demand analgesia for the long-term management of chronic pain. Cells engineered to produce an analgesic in response to spearmint aroma and implanted in mouse models of chronic pain reduce the pain-associated behaviour after oral intake of spearmint essential oil with no adverse effects.