Protein transduction therapy into cochleae via the round window niche in guinea pigs.
Protein transduction therapy into cochleae via the round window niche in guinea pigs.
复制标题
DOI：
10.1038/mtm.2016.55
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Minoda R
中科院分区：
文献类型：
--
作者：
Takeda H;Kurioka T;Kaitsuka T;Tomizawa K;Matsunobu T;Hakim F;Mizutari K;Miwa T;Yamada T;Ise M;Shiotani A;Yumoto E;Minoda R
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.
