Herpes simplex virus-mediated gene transfer as a tool for neuropsychiatric research

There is an enormous initiative to establish causal relationships between brain biology (including patterns of gene expression) and behavior. Unfortunately, genetic intervention is not accomplished easily in the brain. One strategy is to engineer and deliver to the brain specialized viral vectors that carry a gene (or genes) of interest, thereby exploiting the natural ability of viruses to insert genetic information into cells. When delivered to the brain, these vectors cause infected cells to increase expression of the genes of interest. Viral vectors are particularly useful when the goal is to manipulate expression of a single gene in a specific brain region, at a specific time, and in animals that developed normally. There are several types of virus that can be adapted for use as viral vectors, including those based on herpes simplex virus (HSV-1), adenovirus (AV), adeno-associated virus (AAV), and lentivirus. Although each vector has its own unique advantages and disadvantages, this rapidly evolving technology has the potential to revolutionize neuropsychiatric research by offering the opportunity to establish, with anatomical and temporal specificity, causal relations between altered expression of individual gene products and alterations in complex behavior.