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

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. © 2023. Springer Nature Limited.

Citation

Gregory J Salimando, Sébastien Tremblay, Blake A Kimmey, Jia Li, Sophie A Rogers, Jessica A Wojick, Nora M McCall, Lisa M Wooldridge, Amrith Rodrigues, Tito Borner, Kristin L Gardiner, Selwyn S Jayakar, Ilyas Singeç, Clifford J Woolf, Matthew R Hayes, Bart C De Jonghe, F Christian Bennett, Mariko L Bennett, Julie A Blendy, Michael L Platt, Kate Townsend Creasy, William R Renthal, Charu Ramakrishnan, Karl Deisseroth, Gregory Corder. Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types. Nature communications. 2023 Sep 13;14(1):5632

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PMID: 37704594

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