Development of AAV vectors with optimized cell-type specificity and labeling efficiency using cell-type-specific promoters.

Abstract

Adeno-associated virus (AAV) vectors are powerful tools for cell-type-selective gene delivery to the central nervous system and are promising viral vectors for gene therapy. Despite research on the identification and modification of minimal enhancers and promoters for cell-type-specific gene expression, the application of these enhancers/promoters to AAV often has a trade-off between cell-type specificity and labeling efficiency. Here, we attempted to label targeted neuronal populations specifically and efficiently by optimizing genomic components of AAV. As a result, we established an optimized AAV expression cassette for cell-type-selective and robust gene expression in oxytocinergic, serotonergic and dopaminergic neurons. we also achieved application of oxytocinergic-neuron-selective AAV to labeling the axonal projection patterns on a whole-brain scale in wild-type mice. Our results suggest that the optimization of gene cassettes in AAV vectors can be useful for specific and efficient gene expression toward targeted cell types. These strategies may improve the performance of previously established approaches using AAV vectors with cell-type-specific promoters.