Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell® peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell® peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell® peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.
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September 2005
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Research Article|
August 23 2005
Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules
Catherine de Coupade;
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
2To whom correspondence should be addressed, at Diatos S.A. Laboratories, Research Division, 3-5 Impasse Reille, 75014 Paris, France (email cdecoupade@diatos.com).
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Antonio Fittipaldi;
Antonio Fittipaldi
1
†Molecular Medicine Laboratory, International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy
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Vanessa Chagnas;
Vanessa Chagnas
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Matthieu Michel;
Matthieu Michel
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Sophie Carlier;
Sophie Carlier
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Ennio Tasciotti;
Ennio Tasciotti
†Molecular Medicine Laboratory, International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy
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Audrey Darmon;
Audrey Darmon
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Denis Ravel;
Denis Ravel
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Jonathan Kearsey;
Jonathan Kearsey
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Mauro Giacca;
Mauro Giacca
†Molecular Medicine Laboratory, International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy
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Françoise Cailler
Françoise Cailler
*Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France
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Publisher: Portland Press Ltd
Received:
March 09 2005
Revision Received:
April 20 2005
Accepted:
April 29 2005
Accepted Manuscript online:
April 29 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 390 (2): 407–418.
Article history
Received:
March 09 2005
Revision Received:
April 20 2005
Accepted:
April 29 2005
Accepted Manuscript online:
April 29 2005
Citation
Catherine de Coupade, Antonio Fittipaldi, Vanessa Chagnas, Matthieu Michel, Sophie Carlier, Ennio Tasciotti, Audrey Darmon, Denis Ravel, Jonathan Kearsey, Mauro Giacca, Françoise Cailler; Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules. Biochem J 1 September 2005; 390 (2): 407–418. doi: https://doi.org/10.1042/BJ20050401
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