"Translocatory proteins" and "protein transduction domains": a critical analysis of their biological effects and the underlying mechanisms.

It has been suggested that several proteins, termed "translocatory" or "messenger" proteins, can move between living cells-exiting the cell of synthesis via an uncharacterized secretory pathway and entering adjacent cells by a nonendocytic mechanism that is active even at 4 degrees C. These activities, which have been mapped to short, highly basic regions termed "protein transduction domains" (PTDs), have engendered considerable interest in the gene therapy and vaccine research communities. If these proteins, and PTDs, are to be used in human or veterinary medicine, it is vital that the mechanisms underlying their effects be understood. This article presents a critical evaluation of the current literature and describes recent findings that indicate that the effects of these sequences might be explained by well-established biological principles.