Cell penetrating peptides: overview and applications to the delivery of oligonucleotides.
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.
Said Hassane
F
F
UMR 5235 CNRS, Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, 34095, Montpellier Cedex 5, France. fatouma.said-hassane@univ-montp2.fr
Saleh
A F
AF
Abes
R
R
Gait
M J
MJ
Lebleu
Bernard
B
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002477:Cells / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy; D009841:Oligonucleotides / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*
D009841:Oligonucleotides; D010455:Peptides