Pseudotyped lentiviral vectors for tract-targeting and application for the functional control of selective neural circuits

•Pseudotyped lentivectors with fusion glycoproteins enhance retrograde gene transfer.•The vectors have the advantage of functional manipulation of specific neural circuits.•Vector technology promotes the study of the mechanism underlying brain functions.•The technology offers a useful tool for gene therapy of neurological disorders. A lentiviral vector strategy for efficient gene transfer through retrograde axonal transport provides a powerful approach for studying the neural circuit mechanisms that mediate higher level functions of the central nervous system. Pseudotyping of human immunodeficiency virus type-1 with different types of fusion glycoproteins (FuGs), which are composed of segments of rabies virus glycoprotein (RV-G) and vesicular stomatitis virus glycoprotein (VSV-G), enhances the efficiency of retrograde gene transfer in both rodent and non-human primate brains. These pseudotyped lentiviral vectors are classified into two groups, highly efficient retrograde gene transfer (HiRet) and neuron-specific retrograde gene transfer (NeuRet) vectors, based on their properties of gene transduction. Combinatorial use of the pseudotyped vectors with various molecular tools for manipulating neural circuit functions (such as the cell targeting, synaptic silencing, and optogenetic or chemogenetic approaches) enables us to control the function of specific neural circuits, thus leading to a deeper understanding of the mechanism underlying various nervous system functions.