Intracellular delivery of siRNA by cell-penetrating peptides modified with cationic oligopeptides.
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.
Ishihara
Tsutomu
T
DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo 105-8461, Japan. tishihar@kumamoto-u.ac.jp
Goto
Maoko
M
Kodera
Kanae
K
Kanazawa
Hideko
H
Murakami
Yasuko
Y
Mizushima
Yutaka
Y
Higaki
Megumu
M
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
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