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Open AccessReview

Recent Developments in Peptide-Based Nucleic Acid Delivery

Department of Metabolomics, ISAS - Institute for Analytical Sciences, Bunsen-Kirchhoff-Str. 11, 44139 Dortmund, Germany
Institut für Molekulare Medizin, Universitätsklinikum Schleswig-Holstein, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2008, 9(7), 1276-1320;
Received: 31 March 2008 / Revised: 4 June 2008 / Accepted: 14 July 2008 / Published: 16 July 2008
(This article belongs to the Special Issue Nucleic Acid Derivatives in Emerging Technologies)
Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls. View Full-Text
Keywords: cell-penetrating peptides; nucleic acid drugs; nucleic acid delivery; endocytosis cell-penetrating peptides; nucleic acid drugs; nucleic acid delivery; endocytosis
MDPI and ACS Style

Veldhoen, S.; Laufer, S.D.; Restle, T. Recent Developments in Peptide-Based Nucleic Acid Delivery. Int. J. Mol. Sci. 2008, 9, 1276-1320.

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