Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides

The cellular membrane constitutes an effective barrier that offers protection for the complex, yet highly ordered, intracellular environment that defines the cell. Passage of molecules across this barrier is highly regulated and highly restricted, with molecular size being the most significant criteria. Over the last 15 years, a class of small cationic peptides has been discovered that can defy the rules of membrane passage and can gain access to the intracellular environment. Importantly, cellular entrance is also permitted for covalently coupled cargo. The cationic nature of these peptides is crucial for their ability to bind and traverse the anionic cellular membrane. Cell penetrating peptides (CPPs) have been used for the delivery of a wide range of macromolecules including peptides, proteins and antisense oligonucleotides. With the recent advancement and understanding of RNA interference (RNAi), CPPs offer an attractive means for the cellular uptake of double-stranded siRNAs to induce a RNAi response. This review focuses on the potential use of CPPs to deliver siRNA into cells and the implications of this technology for both gene function determination and therapeutic potential.