Direct protein transfer to terminally differentiated muscle cells.

Recently, a new approach for direct protein transfer to mammalian cells based on the herpes simplex virus type 1 protein VP22 has been described. This protein has the remarkable property of intercellular trafficking, which is independent of direct cell contacts and is also retained when fused to heterologous proteins. However, the spreading has only been described for proliferating cells and has also been controversially discussed. In this study we describe the generation of a GFP-VP22 fusion protein which is able to spread in COS-7 cells after transient transfection. Moreover, we show in coculture experiments with transfected COS-7 cells and C2C12 myotubes that this fusion protein is also able to spread into terminally differentiated skeletal muscle cells. These results suggest that VP22 might be a novel therapeutic tool for direct protein transfer not only in proliferating but also in terminally differentiated cells.