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Article Dans Une Revue Nucleic Acids Research Année : 2007

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics

May C Morris
E. Gros
M. Choob
  • Fonction : Auteur
J. Archdeacon
  • Fonction : Auteur

Résumé

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics.
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hal-03107605 , version 1 (22-03-2021)

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May C Morris, E. Gros, Gudrun Aldrian-Herrada, M. Choob, J. Archdeacon, et al.. A non-covalent peptide-based carrier for in vivo delivery of DNA mimics. Nucleic Acids Research, 2007, 35 (7), pp.e49-1-e49-10. ⟨10.1093/nar/gkm053⟩. ⟨hal-03107605⟩
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