Engineering Cell Type Specific Delivery Vectors for Noninvasive Modulation of Brain Circuits and Behaviors

Abstract

Within neuroscience the modulation and monitoring of specific circuits is achieved using a combination of transgenic animals and direct injection of viral vectors. To provide an alternative to invasive brain injection and increase transduction coverage and efficiency, we previously engineered adeno-associated viruses (AAVs) that efficiently cross the BBB in adult mice (Deverman et al, 2016; Chan et al, 2017). When delivering genes systemically, however, it is currently not possible to achieve a high degree of specificity for defined neuronal cell types in specific brain regions without the use of transgenic approaches. Here, we attempt to address this limitation by selectively engineering capsids with regional and cell-type specificity using CREATE, the Cre recombination-dependent AAV targeted evolution (Deverman et al, 2016) methodology that recovers capsids that transduce predefined Cre+ target cell populations.