Programming Membrane Fusion and Subsequent Apoptosis into Mammalian Cells

By the delivery of specific natural or engineered proteins,
mammalian cells can be programmed to perform increasingly sophisticated
and useful functions. Here, we introduce a set of proteins that has
potential value in cell-based therapies by programming a cell to target
tumor cells. First, the delivery of VSV-G (vesicular stomatitis virus
glycoprotein) allowed the cell to undergo membrane fusion with adjacent
cells to form syncytia (i.e., a multinucleated cell) in conditions
of low pH typically occurring at a tumor site. The formation of syncytia
caused the clustering of nuclei along with an integration of the microtubule
network and ER. Interestingly, the formation of syncytia between cells
that are dynamically blebbing, a mode of migration preferred during
tumor metastasis, resulted in the loss of these morphology changes.
Lastly, the codelivery of VSV-G with L57R (an engineered photoactivated
caspase-7) allowed cells to undergo low pH-dependent membrane fusion
followed by blue light-dependent apoptosis. In cell-based therapies,
the clearance of syncytia between tumor cells might further trigger
an immune response against the tumor.