ABSTRACT
It was almost 20 years ago, in 1988, that Frankel and Pabo reported the capture of
HIV-TAT by cells and its transport to the nucleus.1 This finding, although not really
pursued at the time, suggested that transcription factors could be transported
between cells. The underlying concept of messenger proteins was then entirely
developed on the basis of a line of research initiated in 1991 in my laboratory and
that of Joliot.2-4 Indeed, we have demonstrated that several homeoprotein
transcription factors are exchanged between cells and started to identify some
functions associated with this newly discovered mode of signal transduction.5 This
point will be alluded to later and fully developed in chapter 13 of this book. In the
context of this introduction, it is important to identify the two peptidic domains
involved in cell internalization and secretion.6 The internalization domain
corresponds to the 16 amino acid-long third helix of the homeodomain, called
penetratin. This peptide is internalized through an endocytosis-independent
mechanism and is capable of carrying attached cargoes of various sizes and
compositions into the cell interior.7-9
Since then, the family of cell-penetrating peptides (CPPs), also known as
transduction peptides, has increased at a rapid pace. The most emblematic ones are
the objects of specific chapters. Their use as new tools for basic research and as
innovative therapeutic agents is also described in this book. I have no doubt that
many other compounds, peptidic, lipopeptidic, or nonpeptidic, will be described in
the near future and will find original and important applications. Among these
applications, the ability of getting across tight junction epitheliums, in particular at
the level of the intestinal barrier and of the blood-brain barrier, is most exciting.