The University of Virginia (UVA) received a $407,589 Project Grant award from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242). The goal of this 3-year grant is to develop novel adeno-associated virus (AAV) tools with improved Cre-dependent expression to study neural circuits. The research aims to address issues with current Cre-dependent AAV designs that can lead to off-target expression, which confounds interpretation of results. The grant will fund the development and evaluation of an improved "FLEX2" AAV design that reduces spontaneous recombination and undesired promoter activity. Preliminary data demonstrates the FLEX2 approach can effectively target and ablate GABAergic interneurons in the hippocampus, leading to epileptic seizures in mice. Upon completion, the FLEX2 plasmids and AAV particles will be distributed to the research community through a collaboration with Addgene.
Generated 3/4/25, 6:42 AM