Tissue-Specific Cell Penetrating Peptides for Targeted Delivery of Small Interfering RNAs

Abstract

Cell penetrating peptides (CPPs) offer unique and promising solutions to overcome barriers to intracellular delivery of potential therapeutics for a variety of diseases, particularly when used as a delivery method for RNA interference agents such as siRNA. CPP mediated siRNA delivery provides promising therapeutic potential for various pathologies including many different types of cancer as well as other pathologies. Both cell-specific and non-cell-specific CPPs can play roles in transporting several types of cargo into cells, including but not limited to drugs, viral vectors, peptide nucleic acids, nanoparticles, liposomes, and siRNA. CPPs mediate siRNA delivery through a variety of delivery methods, including covalent conjugation and nanoparticle formation, and can be fashioned to facilitate endosomal escape. While no therapeutics currently utilize CPP-mediated siRNA delivery, two major approved therapeutics use RNA interference as a treatment modality, and many clinical trials are in progress testing the use of CPPs, again with an emphasis on the treatment of cancer. Further research is needed before the clinical use of CPP/siRNA complexes is commonplace, but advances in both CPP and siRNA technology appear promising for this method of treatment.