PROTEIN TRANSDUCTION DOMAINS; TARGETED VS. NON-TARGETED TISSUE DELIVERY


Maliha Zahid, M.D., University of Pittsburgh, Pittsburgh, PA, USA

The ability of certain proteins to cross cell membrane barriers was a chance finding reported over 20 years ago. This ability, also termed protein transduction, is localized to 6-30, basic, cationic peptide motifs, known as protein transduction domains (PTDs). In general, PTDs can be classified into 3 types: cationic peptides of 6-12 amino acids in length comprised predominantly of arginine, ornithine and/or lysine residues; hydrophobic peptides such as leader sequences of secreted growth factors and cytokines; and cell-type specific peptides, identified by screening of peptide phage display libraries, also known as phage display or biopanning. These three types of transduction peptides have many different applications including delivery of therapeutic proteins and drugs, delivery of fluorescent or radioactive compounds for imaging, and improving uptake of DNA, RNA and even viral particles. In general the cationic peptides appear to be more efficient but have the drawback of being non-specific. Peptides felt to be tissue specific and identified through screening of large phage libraries appear to be relatively more tissue-specific though at the expense of efficiency. In this review an introduction to PTD technology with focus on phage display as a powerful tool to target tissue, without the need for characterizing the target molecule or receptor apriori, will be presented. In addition the potential for PTDs to serve as diagnostic and therapeutic agents will be high-lighted.