Viral Peptides shuttles for intracellular delivery

Over the past decade, an increasing number of potential drugs have been suggested for therapeutic application. Often bio-macromolecules show a limited ability to cross the plasma membrane resulting in poor cellular access, which largely prevents them from reaching intracellular targets and from crossing epithelial or endothelial barriers. Several approaches have been proposed to overcome such limitations, including micro-injection, electroporation, viral delivery systems, liposomes, encapsulation in polymers, and receptor mediated endocytosis. Unfortunately, these approaches are often plagued with limited efficiency, and high cellular toxicity. The discovery of several peptides with the ability to cross the plasma membrane of eukaryotic cells by a possibly receptor- and endocytosis-independent mechanism, has opened a new avenue in biomedical research. Among the so-called cell penetrating peptides (CPPs), Tat, penetratin and VP22 have been widely used and have shown to be entrapped in intracellular organelles. Thus, one of the main goals of recent research is the obtainment of novel delivery systems that are able to cross membranes without being entrapped in intracellular organelles1. Viral derived peptides, and in particular those derived by viral entry proteins, may be useful as delivery vehicles due to their intrinsic properties of inducing membrane perturbation.The present talk will describe results obtained with the use of a peptide derived from Herpes simplex virus type 1 for the delivery of bioactive molecules or fluorescent dyes inside the host cell. In particular, its use for the intracellular delivery of quantum dots (QDs)2, liposomes3 and nanoparticles will be addressed.