Arginine grafting to endow cell permeability

We report on a means to endow proteins with the ability to permeate mammalian cells without appending an exogenous domain. Our approach is to install a cationic patch on the surface of a target protein by the grafting of arginine residues. Doing so with GFP did not compromise conformational stability but enabled efficient cellular uptake that was dependent on cell-surface glycosaminoglycans. We anticipate that this cell-permeable variant of GFP, which obviates the need for transfection, will be useful for numerous applications in cell biology and that the method of arginine grafting will be broadly applicable.