A non-covalent peptide-based strategy for protein and peptide nucleic acid transduction.
The development of therapeutic peptides and proteins is limited by the poor permeability and the selectivity of the cell membrane. The discovery of protein transduction domains has given a new hope for administration of large proteins and peptides in vivo. We have developed a non-covalent strategy for protein transduction based on an amphipathic peptide, Pep-1, that consists of a hydrophobic domain and a hydrophilic lysine-rich domain. Pep-1 efficiently delivers a variety of fully biologically active peptides and proteins into cells, without the need for prior chemical cross-linking or chemical modifications. The mechanism through which Pep-1 delivers active macromolecules does not involve the endosomal pathway and the dissociation of the Pep-1/macromolecule particle occurs immediately after it crosses the cell membrane. Pep-1 has been successfully applied to the screening of therapeutic peptides in vivo and presents several advantages: stability in physiological buffer, lack of toxicity and of sensitivity to serum. In conclusion, Pep-1 technology could contribute significantly to the development of fundamental and therapeutic applications and be an alternative to covalent protein transduction domain-based technologies.
Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, Department of Molecular Biophysics and Therapeutic, 1919 Route de Mende, 34293 Montpellier, France.
Edwige
E
Gros
Sebastien
S
Deshayes
May C
MC
Morris
Gudrun
G
Aldrian-Herrada
Julien
J
Depollier
Frederic
F
Heitz
Gilles
G
Divita
D000818:Animals; D002478:Cells, Cultured; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
D004337:Drug Carriers; C503924:Pep-1 peptide; D020135:Peptide Nucleic Acids; D010455:Peptides; D011506:Proteins; D003543:Cysteamine