Engineering a pseudotyped lentiviral platform to enable lineage-specific transduction of immune cells

Cell-specific transduction remains one of the next frontiers for virally-delivered gene therapy. Efforts to achieve cell-specific transduction have largely been limited to borrowing of preexisting viral glycoproteins and pseudotyping viral surface envelopes to result in altered tropism. Our lab recently developed a “receptor-blinded” version of VSVG, which we call “VSVGmut”, enabling co-display of a new LV pseudotype ligand to drive specific lentiviral tropism. Initial experiments have shown modularity of this platform for achieving potent transduction of on-target cells via a range of co-expressed host proteins, with minimal infection of bystander cells, across a range of affinities (pM to uM) and at frequencies as low as 1 in 100,000.