Current Pharmaceutical Design - Volume 19, Issue 16, 2013

Since the initial evidence that antennapedia homeobox [1] can cross cell membranes and internalize into cells, numerous peptides with similar translocation properties have been described. These peptides are referred to as cell-penetrating peptides (CPPs) or protein- transduction domains (PTDs). Reviews on reported CPP sequences have been recently published [2,3], together with reviews on their mechanisms of internaliz Read More

Intracellular delivery using cell-penetrating peptides (CPPs) has received considerable attention as a promising method for introducing exogenous molecules into cells. The mechanisms that enable efficient internalization of CPPs together with cargo molecules are also of interest. In this review, we describe our current views of membrane translocation of CPPs, especially those rich in arginine, as these peptides represent one of t Read More

Although siRNA consist in very promising therapeutics, their clinical development is limited by several biological barriers including low cellular permeability, poor stability and lack of tissue specificity. Therefore the Achilles' heel for siRNA-based therapy is directly related to the lack of efficient system to promote their delivery. During the last two decades, cell-penetrating peptides (CPPs) have been widely developed to Read More

The insides of cells can be viewed as a treasure trove of targets for therapeutic intervention of diseases or as deposits for contrasting agents. Increasingly the molecules that need to be delivered to the inside of cells for these purposes are macromolecular and membrane impermeable. Cell penetrating peptides (CPPs) have proven abilities to deliver a range of macromolecular cargo into cells thus raising their profile as p Read More

The increasing knowledge on the genetic basis of disease has allowed the development of promising gene-targeted therapies that can be applied to numerous diseases. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or repair and regulation of specific genes. However, the clinical application of these large and charged molecules remains highly dependent on the de Read More

Cell-penetrating peptides (CPPs) are promising tools for intracellular delivery. However, no consensus regarding their internalization mechanism has been reached within the scientific community. Although endocytosis seems to be the preferred internalization mechanism for most CPP-cargo complexes, examples of direct translocation have also been identified. In this review we go through the several ways of studying CPP-m Read More

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 disc Read More

Duchenne muscular dystrophy is a severe, X-linked muscle wasting disorder caused by the absence of an integral structural protein called dystrophin. This is caused by mutations or deletions in the dystrophin gene which disrupt the reading frame, thereby halting the production of a functional protein. A number of potential therapies have been investigated for the treatment of this disease including utrophin upregulat Read More

Morpholino oligos (Morpholinos) are widely used tools for knocking down gene expression and are currently in a clinical trial for treatment of Duchene muscular dystrophy. A Morpholino analog has been in a clinical trial as a potential anti-bioterrorism agent for inhibiting replication of deadly Marburg viral infection. The cellular uptake of Morpholinos can been greatly increased by conjugation with cell-penetrating peptid Read More

Acute myocardial infarction (AMI) is a frequent and disabling disease, which is the first cause of cardiovascular mortality worldwide. Infarct size is a major determinant of myocardial functional recovery and mortality after AMI. Limitation of infarct size thus appears as an appropriate strategy to prevent post-ischemic heart failure and improve survival. Reperfusion is the only treatment recommended to reduce infarct size but des Read More