Abstract
The development of peptide-drugs and therapeutic proteins is limited by the poor permeability and the selectivity of the cell membrane. We have developed a new peptide-based strategy (Pep-1) for protein transduction into cells. Pep-1 is an amphipathic peptide consisting of a hydrophobic domain and a hydrophilic lysine-rich domain. Pep-1 efficiently delivers a variety of fully biologically active peptides and proteins into cells, without the need for prior chemical cross-linking or denaturation steps. The mechanism through which Pep-1 delivers macromolecules does not involve the endosomal pathway and the dissociation of the Pep-1/macromolecule particle occurs immediately after it crosses the cell membrane. Pep-1 has recently been applied to the screening of therapeutic peptides in vivo and presents several advantages: stability in physiological buffer, lack of toxicity and of sensitivity to serum. Pep-1 technology could contribute significantly to the development of fundamental and therapeutic applications.