Enhancer-Driven Gene Expression (EDGE) Enables the Generation of Viral Vectors Specific to Neuronal Subtypes

Autor: Rajeevkumar Raveendran Nair, Stefan Blankvoort, Maria Jose Lagartos, Cliff Kentros
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 23, Iss 3, Pp - (2020)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.100888
Popis: Summary: Although a variety of remarkable molecular tools for studying neural circuits have recently been developed, the ability to deploy them in particular neuronal subtypes is limited by the fact that native promoters are almost never specific enough. We recently showed that one can generate transgenic mice with anatomical specificity surpassing that of native promoters by combining enhancers uniquely active in particular brain regions with a heterologous minimal promoter, an approach we call EDGE (Enhancer-Driven Gene Expression). Here we extend this strategy to the generation of viral (rAAV) vectors, showing that some EDGE rAAVs can recapitulate the specificity of the corresponding transgenic lines in wild-type animals, even of another species. This approach thus holds the promise of enabling circuit-specific manipulations in wild-type animals, not only enhancing our understanding of brain function, but perhaps one day even providing novel therapeutic avenues to approach disorders of the brain. : Molecular Biology; Neuroscience; Techniques in Neuroscience Subject Areas: Molecular Biology, Neuroscience, Techniques in Neuroscience
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