RNAi and chemogenetic reporter co-regulation in primate striatal interneurons

Walter Lerchner, Abdullah A. Adil, Sekinat Mumuney, Wenliang Wang, Rossella Falcone, Janita Turchi, Barry J. Richmond

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Using genetic tools to study the functional roles of molecularly specified neuronal populations in the primate brain is challenging, primarily because of specificity and verification of virus-mediated targeting. Here, we report a lentivirus-based system that helps improve specificity and verification by (a) targeting a selected molecular mechanism, (b) in vivo reporting of expression, and (c) allowing the option to independently silence all regional neural activity. Specifically, we modulate cholinergic signaling of striatal interneurons by shRNAmir and pair it with hM4Di_CFP, a chemogenetic receptor that can function as an in vivo and in situ reporter. Quantitative analyses by visual and deep-learning assisted methods show an inverse linear relation between hM4Di_CFP and ChAT protein expression for several shRNAmir constructs. This approach successfully applies shRNAmir to modulating gene expression in the primate brain and shows that hM4Di_CFP can act as a readout for this modulation.

Original languageEnglish (US)
Pages (from-to)69-80
Number of pages12
JournalGene Therapy
Issue number1-2
StatePublished - Feb 2022
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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