Evaluation of the cell-penetrating peptide TAT as a trans-blood-brain barrier delivery vehicle

Therapeutic delivery into the brain parenchyma is difficult due to the presence of the blood-brain barrier (BBB). One potential solution is to use cell-penetrating peptides (CPPs). CPPs are short peptides made up of primarily positively charged amino acids that have the ability to transduce cell membranes and deliver cargoes to cells. It is unclear, however, whether CPPs can penetrate cell barriers, such as the BBB, and deliver cargoes into cells on the other side. In this study, we examined the ability of the CPP TAT to deliver a green fluorescent protein (GFP) cargo across an endothelial monolayer. GFP-TAT had only minimal permeability across the monolayer, and the rate was no different from GFP alone or other similarly sized dextrans. Furthermore, this permeability was too small to detect transduction of GFP-TAT into astrocytes on the other side of the monolayer. We conclude that TAT does not have the ability to deliver cargoes across an intact BBB, and therefore may not be a suitable vehicle for therapeutic delivery to the brain.