Rational design and applications of cell-penetrating peptides

Abstract: Cell-penetrating peptides are peptides capable of translocating the cellular membrane and entering the cell, either alone or together with a cargo. Potential applications of cell-penetrating peptides include drug delivery and gene therapy. This thesis is focused on the development of novel cell-penetrating peptides and applications for passage across the blood-brain barrier. We have developed a series of novel cell-penetrating peptides based on the model amphipathic peptide and modifications developed for the PepFect peptides. Our general goal is to improve our understanding of the structural requirements for efficient cell penetration and to apply this knowledge in the development of improved cell-penetrating peptides. We have also developed an in vitro model of the blood brain barrier based on brain endothelial cells grown on a semi-permeable membrane. This model has been used together with a series of novel peptides modified with targeting sequences in order to study the passage of peptides across the barrier and into an underlying layer of glioma cells.