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Int J Mol Sci. 2008 Jun;9(7):1276-320. doi: 10.3390/ijms9071276. Epub 2008 Jul 16.

Recent developments in peptide-based nucleic acid delivery.

Author information

1
Department of Metabolomics, Institute for Analytical Sciences, Dortmund, Germany. veldhoen@isas.de <veldhoen@isas.de>

Abstract

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 cell-penetrating 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 antisense-oligonucleotides), 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.

KEYWORDS:

CLSM, confocal laser scanning microscopy; CPP, cell-penetrating peptide; EIPA, ethylisopropylamiloride; FCS, fetal calf serum; GFP, green fluorescent protein; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HIV, human immunodeficiency virus; IFN, interferon; IL, interleukin; LF, Lipofectamine™; LF2000, Lipofectamine™ 2000; MAP, model amphipathic peptide; MEND, multifunctional envelope-type nano device; NLS, nuclear localisation sequence; OMe, O-methyl; PAMAM, polyamidoamine; PEG, polyethylene glycol; PEI, polyethyleneimine; PMO, phosphorodiamidate morpholino oligomer; PNA, peptide nucleic acid; PTD, protein transduction domains; RNAi, RNA interference; SAP, Sweet Arrow Peptide; STR-R8, stearyl-R8; TAR, transactivator responsive region; TFO, triplex forming oligonucleotide; TLR9, toll-like receptor 9; TNF, tumour necrosis factor; TP10, transportan 10; bPrPp, bovine prion protein derived peptide; cell-penetrating peptides; endocytosis; hCT, human calcitonin; mPrPp, murine prion protein derived peptide; miRNA, microRNA; nucleic acid delivery; nucleic acid drugs; siRNA, small inhibitory RNA

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