Direct protein transfer to terminally differentiated muscle cells

Recently, a new approach for direct protein transfer to mammalian cells bas ed 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 het erologous proteins. However, the spreading has only been described for prol iferating cells and has also been controversially discussed. In this study we describe the generation of a GFP-VP22 fusion protein which is able to sp read in COS-7 cells after transient transfection. Moreover, we show in cocu lture experiments with transfected COS-7 cells and C2C12 myotubes that this fusion protein is also able to spread into terminally differentiated skele tal muscle cells. These results suggest that VP22 might be a novel therapeu tic tool for direct protein transfer not only in proliferating but also in terminally differentiated cells.