title: Intracellular delivery of siRNA by cell-penetrating peptides modified with cationic oligopeptides.
abstract: To achieve the effective intracellular delivery of siRNA and silence specific genes, various types of conjugates between cell-penetrating peptides (CPPs; Transportan, Penetratin, Tat) and cationic peptides were developed. Uptake, intracellular localization, cytotoxicity, and biological activity of siRNA were significantly dependent on the kind of CPP used and the length of the cationic peptides in the conjugate. Transportan-based conjugates yielded both high internalization of siRNA and strong gene silencing activity, while Penetratin- and Tat-based conjugates did not. These different properties of CPPs emphasize the importance of careful peptide selection and design when attempting the application of CPP technology.
authors.affiliation: DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo 105-8461, Japan. tishihar@kumamoto-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Maoko
authors.initials: M
authors.lastname: Goto
authors.forename: Kanae
authors.initials: K
authors.lastname: Kodera
authors.forename: Hideko
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
authors.forename: Megumu
authors.initials: M
authors.lastname: Higaki
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides; D016503:Drug Delivery Systems; D019004:Galanin / Q000737:chemistry; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014862:Wasp Venoms / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; D010455:Peptides; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C110068:transportan; D019004:Galanin; C414409:penetratin; D008156:Luciferases