Protein and peptide transduction, twenty years later a happy birthday.

This commentary underscores the following aspects of Cell Permeable Peptides/Transduction Peptides (CPP/PTD) research. First the discovery of CPP/PTD takes its origin in the observation that some full-length transcription factors navigate between cells. The latter physiological origin is of interest as the significance of this new mode of signal transduction is not yet fully understood. A second point is that most breakthroughs in the domain have been made possible by long lasting collaborations between biologists, chemists and physicists. It is beyond doubt that the understanding of the mechanisms of secretion and internalization, in parallel with the development of new transduction compounds, not only peptides, will require that such collaborative efforts be amplified. Finally, although the domain is flourishing and our minds full of hope, it must be said that many points need to be resolved before getting close to bedside. Among these points are bio-disponibility, toxicity and specific addressing to body regions, cell types and intracellular compartments. In brief, beyond this happy birthday, there is still plenty of home work!