| Title: | Treatment of chronic pain by designer cells controlled by spearmint aromatherapy |
| Author(s): | Wang H; Xie M; Charpin-El Hamri G; Ye H; Fussenegger M; |
| Address: | "Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. Departement Genie Biologique, Institut Universitaire de Technologie, IUT, Villeurbanne, France. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. fussenegger@bsse.ethz.ch. Faculty of Science, University of Basel, Basel, Switzerland. fussenegger@bsse.ethz.ch" |
| DOI: | 10.1038/s41551-018-0192-3 |
| ISSN/ISBN: | 2157-846X (Electronic) 2157-846X (Linking) |
| 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 Na(V)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" |
| Keywords: | "Animals *Aromatherapy Female Formaldehyde/toxicity HEK293 Cells Humans Mentha spicata/*chemistry/metabolism Mice Mice, Inbred C57BL NAV1.7 Voltage-Gated Sodium Channel/genetics/metabolism Neuralgia/chemically induced/metabolism/*therapy Odorants Oils, Vol;" |
| Notes: | "MedlineWang, Hui Xie, Mingqi Charpin-El Hamri, Ghislaine Ye, Haifeng Fussenegger, Martin eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2018/02/01 Nat Biomed Eng. 2018 Feb; 2(2):114-123. doi: 10.1038/s41551-018-0192-3. Epub 2018 Feb 6" |
