title: Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules.
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.
authors.affiliation: Diatos S.A., 166 Boulevard du Montparnasse, 75014 Paris, France. cdecoupade@diatos.com
authors.forename: Catherine
authors.initials: C
authors.lastname: De Coupade
authors.forename: Antonio
authors.initials: A
authors.lastname: Fittipaldi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Chagnas
authors.forename: Matthieu
authors.initials: M
authors.lastname: Michel
authors.forename: Sophie
authors.initials: S
authors.lastname: Carlier
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.forename: Audrey
authors.initials: A
authors.lastname: Darmon
authors.forename: Denis
authors.initials: D
authors.lastname: Ravel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kearsey
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Françoise
authors.initials: F
authors.lastname: Cailler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001287:Attachment Sites, Microbiological / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D019426:Integrases / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D013696:Temperature; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011994:Recombinant Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases