Dendritic cell-targeted lentiviral vector development
Lentiviral vectors have been useful in research and for gene therapy because of their ability to stably express genes in a wide variety of target cell-types. However, lentiviral vectors don’t work well in DCs because they are blocked by SAMHD1. To overcome this block to DC transduction, we devised HIV-1-based lentiviral vectors that package SIV Vpx resulting in a two-log increase in titer on DCs. This high efficiency transduction provides a means by which DCs can be used in gene therapy. In addition, the vectors encode various immunostimulatory genes that induce the DCs to secrete T cell activating cytokines that will increase the strength of the immune response. Through these studies, we are learning how DCs function and how they can be engineered to stimulate antigen-specific T cells.