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Cell penetrating peptides: overview and applications to the delivery of oligonucleotides

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Abstract

Crossing biological barriers represents a major limitation for clinical applications of biomolecules such as nucleic acids, peptides or proteins. Cell penetrating peptides (CPP), also named protein transduction domains, comprise short and usually basic amino acids-rich peptides originating from proteins able to cross biological barriers, such as the viral Tat protein, or are rationally designed. They have emerged as a new class of non-viral vectors allowing the delivery of various biomolecules across biological barriers from low molecular weight drugs to nanosized particles. Encouraging data with CPP-conjugated oligonucleotides have been obtained both in vitro and in vivo in animal models of diseases such as Duchenne muscular dystrophy. Whether CPP-cargo conjugates enter cells by direct translocation across the plasma membrane or by endocytosis remains controversial. In many instances, however, endosomal escape appears as a major limitation of this new delivery strategy.

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Acknowledgments

Work in the authors' laboratories has been financed by grants from AFM (Association Française contre les Myopathies), ANR (Agence Nationale de la Recherche) and LNFCC (Ligue Nationale de Lutte contre le Cancer). A.F. Saleh is supported by a Development Gap Fund grant from MRC-Technology and we acknowledge additional funding from Action Duchenne. We thank A.A. Arzumanov, D. Williams and D. Owen for their work in synthesis and activity of PNA-peptide and PMO-peptide conjugates. We also thank H. Yin and M. Wood (University of Oxford) for providing information and figures regarding in vivo mdx mouse studies in DMD.

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  1. UMR 5235 CNRS, Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, 34095, Montpellier Cedex 5, France

    F. Said Hassane, R. Abes & Bernard Lebleu

  2. Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge, CB2 0QH, UK

    A. F. Saleh & M. J. Gait

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  1. F. Said Hassane
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  2. A. F. Saleh
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  3. R. Abes
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Correspondence to F. Said Hassane or Bernard Lebleu.

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Said Hassane, F., Saleh, A.F., Abes, R. et al. Cell penetrating peptides: overview and applications to the delivery of oligonucleotides. Cell. Mol. Life Sci. 67, 715–726 (2010). https://doi.org/10.1007/s00018-009-0186-0

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  • DOI: https://doi.org/10.1007/s00018-009-0186-0

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