title: Chemically modified cell-penetrating peptides for the delivery of nucleic acids.
abstract: Short nucleic acids targeting biologically important RNAs and plasmids have been shown to be promising future therapeutics; however, their hydrophilic nature greatly limits their utility in clinics and therefore efficient delivery vectors are greatly needed. Cell-penetrating peptides (CPPs) are relatively short amphipathic and/or cationic peptides that are able to transport various biologically active molecules inside mammalian cells, both in vitro and in vivo, in a seemingly non-toxic fashion. Although CPPs have proved to be appealing drug delivery vehicles, their major limitation in nucleic acid delivery is that most of the internalized peptide-cargo is entrapped in endosomal compartments following endocytosis and the bioavailability is therefore severely reduced. Several groups are working towards overcoming this obstacle and this review highlights the evidence that by introducing chemical modification in CPPs, the bioavailability of delivered nucleic acids increases significantly.
authors.affiliation: Stockholm University, Department of Neurochemistry, Arrhenius Laboratories for Natural Sciences, S-10691 Stockholm, Sweden. maarja.mae@ki.se
authors.forename: Maarja
authors.initials: M
authors.lastname: Mäe
authors.forename: Samir El
authors.initials: SE
authors.lastname: Andaloussi
authors.forename: Taavi
authors.initials: T
authors.lastname: Lehto
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics) / Q000627:therapeutic use*; D001682:Biological Availability; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D018014:Gene Transfer Techniques; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D016375:Antisense Elements (Genetics); D004337:Drug Carriers; D010455:Peptides; D013501:Surface-Active Agents