siRNA-induced RNA Interference (RNAi) responses have great potential to treat human disease; however, siRNAs are highly charged macromolecules with no ability to enter cells and require a delivery agent. Peptide Transduction Domains (PTDs), also called Cell Penetrating Peptides (CPPs), are delivery peptides with the potential to deliver macromolecular peptides, proteins and siRNAs into cells. Here we discuss the multitude of ways that PTDs/CPPs have been utilized to deliver siRNAs from direct conjugates to complex nanoparticles. PTD/CPP-mediated siRNA delivery has come a long way and has great potential to address the siRNA delivery problem.
Keywords: PTD, CPP, siRNA, RNAi, nanoparticles, cell deliverY, macropinocytosis