TAT-based drug delivery system--new directions in protein delivery for new hopes?

There has been great progress in the use of TAT-based drug delivery systems for the delivery of different macromolecules into cells in vitro and in vivo, thus circumventing the bioavailability barrier that is a problem for so many drugs. There are many advantages to using this system, such as the ability to deliver these cargoes into all types of cells in culture and into all organs in vivo. This system can even deliver cargoes into the brain across the blood-brain barrier. In addition, the ability to target specific intracellular sub-localizations such as the nuclei, the mitochondria and lysosomes further expands the possibilities of this drug delivery system to the development of sub-cellular organelle-targeted therapy. The therapeutic applications seem almost unlimited, and the use of the TAT-based delivery system has extended from proteins to a large variety of cargoes such as oligonucleotides, imaging agents, low molecular mass drugs, nanoparticles, micelles and liposomes. In this review the most recent advances in the use of the TAT-based drug delivery system will be described, mainly discussing TAT-mediated protein delivery and the use of the TAT system for enzyme replacement therapy.