Anti-OR1A1 monoclonal antibody Made to order

The vast number of detectable odors makes matching olfactory receptors (ORs) to their ligands a daunting task. Krautwurst and colleagues have hypothesized that this process can be simplified by focusing on those odorants that are perceptually relevant food odors. In this issue of Chemical Senses, they use this framework to identify highly sensitive receptors for 2 key food odorants found in red wine and onions, that activate broadly tuned OR1A1 and narrowly tuned OR2M3, respectively. This work provides further evidence for the advantage of screening receptors against ecologically relevant odors, and we discuss it in the context of current limitations in OR screening methods.

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.