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

Abstract

Although a variety of remarkable molecular tools for studying neural circuits have recently beendeveloped, the ability to deploy them in particular neuronal subtypes is limited by the fact that nativepromoters are almost never specific enough. We recently showed that one can generate transgenicmice with anatomical specificity surpassing that of native promoters by combining enhancers uniquelyactive 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 trans-genic lines in wild-type animals, even of another species. This approach thus holds the promise ofenabling circuit-specific manipulations in wild-type animals, not only enhancing our understandingof brain function, but perhaps one day even providing novel therapeutic avenues to approach disor-ders of the brain