Snyder, EL and Dowdy, SF. Recent advances in the use of protein transduction domains for the delivery of peptides, proteins and nucleic acids in vivo. Expert Opin Drug Deliv 2: 43-51

UCSD School of Medicine, Howard Hughes Medical Institute and Department of Cellular & Molecular Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, USA.
Expert Opinion on Drug Delivery (Impact Factor: 4.84). 02/2005; 2(1):43-51. DOI: 10.1517/17425247.2.1.43
Source: PubMed


Protein transduction domains (PTDs) are small cationic peptides that can facilitate the uptake of large, biologically active molecules into mammalian cells. Recent reports have shown that PTDs can mediate the delivery of cargo to tissues throughout a living organism. Such technology could eliminate the size restrictions on usable drugs, so enabling previously unavailable large molecules to modulate in vivo biology and alleviate disease. This article will review the evidence that PTDs can be used both to deliver active molecules to pathological tissue in vivo and to treat models of disease such as cancer, ischaemia and inflammation.

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    • "In addition, they can carry wide varieties of biologically active macromolecules into mammalian cells with higher efficiency, specific targeting, and most importantly absence of cytotoxicity (Fenton et al., 1998; Snyder and Dowdy, 2005). Currently, many synthetic CPPs are employed to deliver different macromolecules such as peptides, proteins, nucleic acids, liposomes, carbohydrates, drugs, nanoparticles, fluorochrome, and quantum dot into mammalian cells (Joliot and Prochiantz, 2004; Schwarze et al., 1999; Snyder and Dowdy, 2005) for therapeutic and other clinical applications. While most of the translocation studies up-to-date have been done in mammalian cells, very few studies have been executed in non-mammalian cells, such as plants (Chugh and Eudes, 2008), fungi (Holm et al., 2005), bacteria (Liu et al., 2008), and microalgae (Hyman et al., 2012). "
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    ABSTRACT: Engineering of algal cells by delivering macromolecules through cell wall and plasma membrane presents many difficulties with the conventional methods. Recent research has shown that a new delivery method, namely cell penetrating peptide (CPP), has the ability to translocate into animal, plant, fungal, and bacterial cells. This study reports the apparent translocation of CPPs into algal cells of Chlamydomonas reinhardtii and the successful delivery of the conjugated fluorochrome. Although translocation efficiency was specific to each CPP studied, pVEC (peptide vascular endothelial cadherin) showed the highest translocation efficiency in comparison with penetratin (PEN), trans-activating transcriptional (TAT) peptide, and transportan (TRA). The maximum translocation of pVEC into the algal cell was reached in 15 min of incubation at 25°C. More importantly, translocation with pVEC demonstrated an absence of cytotoxicity. Thus, we suggested that pVEC is an attractive candidate for delivering macromolecules into algal cells for use in industrial applications. Biotechnol. Bioeng. © 2013 Wiley Periodicals, Inc.
    Biotechnology and Bioengineering 10/2013; 110(10). DOI:10.1002/bit.24935 · 4.13 Impact Factor
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    • "CPPs are of different sizes and amino acid sequences but with one distinct feature, which is capable to deliver various cargo molecules across the plasma membrane,some even can cross BBB to facilitate the delivery of various therapeutic molecules; thus, they act as molecular delivery vehicles (Fig. 1) [60]. A number of CPPs have already shown great ability in improving therapeutic molecule delivery across the BBB to treat CNS diseases [61]. The CPPs used include TAT, Angiopep, penetratin, TP, rabies virus glycoprotein (RVG), prion peptide, and SynB [62-67]. "
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    ABSTRACT: The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the entry of unwanted substances - pathogens and therapeutic molecules alike - into the central nervous system (CNS) from the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes. However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules have limited use in treating neurological diseases. Finding effective, safe, and convenient ways to deliver therapeutic molecules into the CNS is thus urgently required. In recent decades, much effort has been expended in the development of drug delivery technologies, of which cell-penetrating peptides (CPPs) have the most promising potential. The present review covers the latest advances in CPP delivery technology, and provides an update on their use in CNS-targeted drug delivery.
    Current Neuropharmacology 03/2013; 11(2):197-208. DOI:10.2174/1570159X11311020006 · 3.05 Impact Factor
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    • "Proofs-of-concept of the CPPs in vivo application for the delivery of small peptides and large proteins and for delivery of PNAs using the chimeric peptide Transportan, derived form the N-terminal fragment of the neuropeptide galanin, linked to mastoparan, a wasp venom peptide was a great breakthrough. Other CPPs that could trigger the movement of a therapeutic agent across the cell membrane into the cytoplasm are continually being designed [5,6]. "
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    ABSTRACT: The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development.
    12/2012; 163(163). DOI:10.3390/biom2020187
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