title: Functional peptide nanocarriers for delivery of novel anti-RelA RNA interference agents as a topical treatment of atopic dermatitis.
abstract: Small interfering RNAs (siRNAs) are a potential treatment of atopic dermatitis (AD) because they can specifically silence the gene expression of AD-related factors. However, siRNA alone cannot exert a sufficiently strong therapeutic effect due to low delivery efficiency to the target tissues and cells; simply increasing the amount used is not possible due to the possibility of off-target effects. We previously reported a novel class of therapeutic RNA interference (RNAi) agents called nkRNA(®) and PnkRNA(®), which have been shown to be effective in several disease models, have greater resistance to nuclease degradation than canonical siRNAs, and do not induce any immunotoxicity. In the present study, we describe a non-invasive and effective transdermal RNAi therapeutic system for atopic dermatitis that uses the functional cell-penetrating stearoyl-oligopeptide OK-102 as a cytoplasm-responsive nanocarrier for nkRNA(®) and PnkRNA(®). The two RNAi agents were targeted against RelA, a subclass of NF-κB (nuclear factor kappa B), and, as part of OK-102 complexes, they strongly silenced RelA mRNA in macrophage cells and demonstrated a significant therapeutic effect in a mouse model of AD. It was shown that OK-102-complexed RNAi agents were an efficient therapeutic system for AD and caused no adverse reactions.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: kanazawa@toyaku.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanazawa
authors.affiliation: BONAC Corporation, Kurume, Fukuoka 839-0861, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Endo
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Tamano
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sogabe
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Seta
authors.affiliation: BONAC Corporation, Kurume, Fukuoka 839-0861, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Ohgi
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Okada DDS Research Institute, Inc., Hachioji, Tokyo 192-0375, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okada
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D003876:Dermatitis, Atopic / Q000276:immunology / Q000628:therapy*; D004139:Dinitrofluorobenzene; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides; D012313:RNA / Q000008:administration & dosage* / Q000737:chemistry; D034622:RNA Interference; D051996:Transcription Factor RelA / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D057846:Cell-Penetrating Peptides; D015850:Interleukin-6; D009842:Oligopeptides; D010455:Peptides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D012313:RNA; D004139:Dinitrofluorobenzene
keywords: Atopic dermatitis; Cytoplasm-responsive peptide carrier; NF-κB RelA; PnkRNA(®); RNAi agents; nkRNA(®)