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Vol 42(2008) N 2 p. 253-260; G.A. Posypanova1,2, A.N. Chuvilin3, N.N. Kireeva4, E.S. Severin2,4, G.E. Pozmogova2,3 Complexes of telomeric oligonucleotides with the PGEk protein vector: Internalization by target cells and antiproliferative activity 1Institute of Molecular Medicine, Sechenov Moscow Medical Academy, Moscow, 119435, Russia2Bioinzheneriya Center, Russian Academy of Sciences, Moscow, 117312, Russia 3Institute of Physicochemical Medicine, Ministry of Health of the Russian Federation, Moscow, 119992, Russia 4All-Russian Center of Molecular Diagnosis and Therapy, Moscow, 117638, Russia Received - 2007-09-20; Accepted - 2007-10-11 Recombinant protein PGEk, consisting of the human epidermal growth factor (hEGF) and a DNA-binding domain, proved to be capable of interacting with the hEGF receptor and inducing cell proliferation, as characteristic of hEGF. PGEk complexes with the telomere-mimic oligonucleotide d(TTAGGG)4 (TMO) and its thio analog (TMS) were efficiently and selectively internalized by cells with a high-level expression of the hEGF receptors. The extent of internalization was studied as a function of the PGEk: oligonucleotide ratio in the complex. The intracellular location of the oligonucleotides was determined. PGEk was found to ensure a more efficient delivery of the oligonucleotides and to protect them from nuclease degradation. The oligonucleotides contained in the complexes exerted a far greater cytotoxic effect as compared with the free oligonucleotides. protein vectors, targeted DNA delivery, oligonucleotides, telomerase, protein-nucleic acid complexes, epidermal growth factor |
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