Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules

Catherine De Coupade, Antonio Fittipaldi, Vanessa Chagnas, Matthieu Michel, Sophie Carlier, Ennio Tasciotti, Audrey Darmon, Denis Ravel, Jonathan Kearsey, Mauro Giacca, Françoise Cailler

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-418
Number of pages12
JournalBiochemical Journal
Volume390
Issue number2
DOIs
StatePublished - Sep 1 2005

Keywords

  • Cell-penetrating peptide
  • Delivery vector
  • Membrane translocation
  • Proteoglycan
  • Tat peptide
  • Therapeutic drug delivery

ASJC Scopus subject areas

  • Biochemistry

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