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Nucleic Acids Research Advance Access originally published online on March 5, 2007
Nucleic Acids Research 2007 35(7):e49; doi:10.1093/nar/gkm053
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Nucleic Acids Research, 2007, Vol. 35, No. 7 e49
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Methods Online

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

May C. Morris1, Edwige Gros1, Gudrun Aldrian-Herrada1, Michael Choob2, John Archdeacon2, Frederic Heitz1 and Gilles Divita1,*

1Centre de Recherches en Biochimie Macromoléculaire, Department of Molecular Biophysics and Therapeutics, FRE-2593 CNRS, 1919 Route de Mende, 34293 Montpellier, France and 2Active Motif, Carlsbad, California, USA

*To whom correspondence should be addressed. Tel: +33 04 67 61 33 92; Fax: +33 04 67 52 15 59; Email: gilles.divita{at}crbm.cnrs.fr

Received October 4, 2006. Revised January 16, 2007. Accepted January 17, 2007.

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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