Recent developments in applications of cell-penetrating peptides – Uptake mechanisms and oligonucleotide delivery
Here we report on recent developments in cell-penetrating peptide mediated delivery of siRNA and other oligonucleotides. We also report on the latest discoveries regarding the debated uptake mechanism of cell-penetrating peptides. For the first time evidence of a cell surface receptor involvement in the uptake of cell-penetrating peptide/oligonucleotide complexes has been described, indicating that properties of the cargo are likely crucial for which pathway is responsible for uptake.
Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate cellular membranes and also bring cargo across with them, they are usually either cationic or amphipathic (1). In recent years cell-penetrating peptides have been used to deliver a multitude of cargoes ranging from quantum dots and nanoparticles to proteins, oligonucleotides and small molecules (2). One of the most interesting developments has been the delivery of non-covalently complexed oligonucleotide cargoes, including plasmids, antisense oligonucleotides and siRNA, both in vitro and in vivo. Another topic of current interest is the much debated mechanism of cellular entry (3). Oligonucleotide delivery and uptake mechanisms are the two topics that will be the focus of this review.
Loss-of-function in a gene is not only associated with hereditary diseases such a haemophilia, cystic fibrosis and muscular dystrophy but it is also implicated in several cancers. A treatment that could possibly restore the correct phenotype is delivery of plasmid DNA (pDNA) containing a functional gene. Additionally, ...