However, furin is expressed by all cells and tissues. In this way, we can redesign immunotoxins to be more selective for killing cancer cells. The toxin is delivered to an acidic endosomal compartment where it is cleaved by a furin-like protease to generate two large fragments. Translocation requires the reduction of the disulfide bond linking the two fragments and also the presence of a KDEL-like sequence at the C terminus. Currently, we are trying to understand the mechanism of cell-mediated toxin reduction.
Several projects are underway that use toxin sequences for the development of therapeutic agents.
To produce an HIV vaccine, we are using nonlethal PE as an immunogenic carrier for the V3 loop of gp120. The translocating domain of PE is being investigated for its ability to increase the efficiency of DNA transfer. FitzGerald, DJ et al. Chiron, MF et al. Mansfield, E et al.