I am a
Home I AM A Search Login

Papers of the Week

Papers: 9 Sep 2023 - 15 Sep 2023

Basic Science, Methodology, Resource

Animal Studies, Human Studies, In Vitro Studies, Molecular/Cellular, Pharmacology/Drug Development

2023 Sep 13

Nat Commun




Editor's Pick

Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types.


Salimando GJ, Tremblay S, Kimmey BA, Li J, Rogers SA, Wojick JA, McCall NM, Wooldridge LM, Rodrigues A, Borner T, Gardiner KL, Jayakar SS, Singeç I, Woolf CJ, Hayes MR, De Jonghe BC, Bennett FC, Bennett ML, Blendy JA, Platt ML, Creasy KT, Renthal WR, Ramakrishnan C, Deisseroth K, Corder G


With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target and manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools and transgenic models for gaining long-term genetic access to MOR+ neural cell types and circuits involved in modulating pain, analgesia and addiction across species are limited. To address this, we developed a catalog of MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression in MOR+ cells. MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. The use of mMORp for in vivo fiber photometry, behavioral chemogenetics, and intersectional genetic strategies is also demonstrated. Lastly, a human designed MORp (hMORp) efficiently transduced macaque cortical OPRM1+ cells. Together, our MORp toolkit provides researchers cell type specific genetic access to target and functionally manipulate mu-opioidergic neurons across a range of vertebrate species and translational models for pain, addiction, and neuropsychiatric disorders.