Biological applications of protein transduction technology

Abstract

The impermeable nature of the cell membrane to peptides, proteins, DNA and oligonucleotides limits the therapeutic potential of these biological agents. However, the recent discovery of short cationic peptides that cross the plasma membrane efficiently is opening up new possibilities for the intracellular delivery of such agents. These peptides are commonly referred to as protein transduction domains (PTDs) and are successfully used to transport heterologous proteins, peptides and other types of cargo into cells. Several recent reports have used the membrane transducing technology in vivo to deliver biologically active cargo into various tissues. This review discusses the structure of the most commonly used PTDs and how their ability to transduce membranes is used to regulate biological functions. It also considers future directions and the potential of this technology to move from the laboratory into the clinic.

Figure 1

A three-step model of membrane transduction by cationic peptides. Step 1: electrostatic interactions between the positively charged protein transduction domain (PTD) (red +) and negative charges on the cell membrane (black −) promote binding of PTD to the cell surface. Step 2: the PTD penetrates the plasma membrane through an as-yet unknown mechanism, towing its attached cargo. Alternatively, the PTD–cargo complex is endocytosed by the cell. Step 3: intracellular delivery of the PTD–cargo complex.