A versatile viral toolkit for functional discovery in the nervous system

Gabrielle Pouchelon, Josselyn Vergara, Justin McMahon, Bram L. Gorissen, Jessica D. Lin, Douglas Vormstein-Schneider, Jason L. Niehaus, Timothy J. Burbridge, Jason C. Wester, Mia Sherer, Marian Fernandez-Otero, Kathryn C. Allaway, Kenneth Pelkey, Ramesh Chittajallu, Chris J. McBain, Melina Fan, Jason S. Nasse, Gregg A. Wildenberg, Gordon Fishell, Jordane Dimidschstein

Research output: Contribution to journalArticlepeer-review


The ability to precisely control transgene expression is essential for basic research and clinical applications. Adeno-associated viruses (AAVs) are non-pathogenic and can be used to drive stable expression in virtually any tissue, cell type, or species, but their limited genomic payload results in a trade-off between the transgenes that can be incorporated and the complexity of the regulatory elements controlling their expression. Resolving these competing imperatives in complex experiments inevitably results in compromises. Here, we assemble an optimized viral toolkit (VTK) that addresses these limitations and allows for efficient combinatorial targeting of cell types. Moreover, their modular design explicitly enables further refinements. We achieve this in compact vectors by integrating structural improvements of AAV vectors with innovative molecular tools. We illustrate the potential of this approach through a systematic demonstration of their utility for targeting cell types and querying their biology using a wide array of genetically encoded tools.

Original languageEnglish (US)
Article number100225
JournalCell Reports Methods
Issue number6
StatePublished - Jun 20 2022


  • AAV
  • circuits
  • neuroscience
  • vector

ASJC Scopus subject areas

  • Genetics
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Biotechnology
  • Computer Science Applications


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