OVERVIEW DELIVERY OF PROTEINS AND PEPTIDES INTO LIVE CELLS BY MEANS OF PROTEIN TRANSDUCTION DOMAINS: POTENTIAL APPLICATION TO ORGAN AND CELL TRANSPLANTATION

Proteins are primary targets in drug discovery. However, with a few rare exceptions, they are unable to cross cell membranes, a limitation that prevents the full exploitation of their therapeutic potential. Major advances have been re-cently made through a novel approach of protein and peptide delivery into cells known as protein transduction or protein therapy. Proteins and peptides can be directly transferred to cells when covalently linked to protein transduction domains (PTD), small peptides that can freely cross cell membranes with low lytic activity (1–3). The mechanism of cellular trans-location of PTD are currently poorly understood. Most of the PTD described in the literature have a high content of basic residues. It is believed that the interaction with the negative cell membrane environment has an important role in the translocation process, and the mechanism of cell internaliza