title: Protein transduction therapy into cochleae via the round window niche in guinea pigs.
abstract: Cell-penetrating peptides (CPPs) are short sequences of amino acids that facilitate the penetration of conjugated cargoes across mammalian cell membranes, and as such, they may provide a safe and effective method for drug delivery to the inner ear. Simple polyarginine peptides have been shown to induce significantly higher cell penetration rates among CPPs. Herein, we show that a peptide consisting of nine arginines ("9R") effectively delivered enhanced green fluorescent protein (EGFP) into guinea pig cochleae via the round window niche without causing any deterioration in auditory function. A second application, 24 hours after the first, prolonged the presence of EGFP. To assess the feasibility of protein transduction using 9R-CPPs via the round window, we used "X-linked inhibitor of apoptosis protein" (XIAP) bonded to a 9R peptide (XIAP-9R). XIAP-9R treatment prior to acoustic trauma significantly reduced putative hearing loss and the number of apoptotic hair cells loss in the cochleae. Thus, the topical application of molecules fused to 9R-CPPs may be a simple and promising strategy for treating inner ear diseases.
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Hiroki
authors: H
authors: Takeda
authors: Department of Otolaryngology, National Defense Medical College , Tokorozawa, Japan.
authors: Takaomi
authors: T
authors: Kurioka
authors: Department of Molecular Physiology, Kumamoto University , Kumamoto, Japan.
authors: Taku
authors: T
authors: Kaitsuka
authors: Department of Molecular Physiology, Kumamoto University , Kumamoto, Japan.
authors: Kazuhito
authors: K
authors: Tomizawa
authors: Department of Otolaryngology, National Defense Medical College , Tokorozawa, Japan.
authors: Takeshi
authors: T
authors: Matsunobu
authors: Department of Molecular Physiology, Kumamoto University , Kumamoto, Japan.
authors: Farzana
authors: F
authors: Hakim
authors: Department of Otolaryngology, National Defense Medical College , Tokorozawa, Japan.
authors: Kunio
authors: K
authors: Mizutari
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Toru
authors: T
authors: Miwa
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Takao
authors: T
authors: Yamada
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Momoko
authors: M
authors: Ise
authors: Department of Otolaryngology, National Defense Medical College , Tokorozawa, Japan.
authors: Akihiro
authors: A
authors: Shiotani
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Eiji
authors: E
authors: Yumoto
authors: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University , Kumamoto, Japan ;
authors: Ryosei
authors: R
authors: Minoda