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Novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells

Abstract

One of the urgent problems of gene therapy is the search for an effective transfection methods. Synthetic cationic peptides (CP) are considered as one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have got significant advantages as gene delivery vehicles by having the virtue of non-natural Ɛ-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for potential clinical application of CPs. In further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particulary LTP, an arginine rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by Dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5-LTP/siRNA complexes have got a resonable tropism to lung tissues.

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Publication details

The article was received on 20 Aug 2018, accepted on 12 Oct 2018 and first published on 13 Oct 2018


Article type: Paper
DOI: 10.1039/C8OB02039F
Citation: Org. Biomol. Chem., 2018, Accepted Manuscript
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    Novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells

    K. V. Kozhikhova, S. M. Andreev, I. P. Shilovskiy, A. V. Timofeeva, A. R. Gaisina, A. A. Shatilov, E. A. Turetskiy, I. M. Andreev, V. V. Smirnov , A. S. Dvornikov and M. R. Khaitov, Org. Biomol. Chem., 2018, Accepted Manuscript , DOI: 10.1039/C8OB02039F

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