論文

査読有り 国際誌
2016年

Protein transduction therapy into cochleae via the round window niche in guinea pigs.

Molecular therapy. Methods & clinical development
  • Hiroki Takeda
  • ,
  • Takaomi Kurioka
  • ,
  • Taku Kaitsuka
  • ,
  • Kazuhito Tomizawa
  • ,
  • Takeshi Matsunobu
  • ,
  • Farzana Hakim
  • ,
  • Kunio Mizutari
  • ,
  • Toru Miwa
  • ,
  • Takao Yamada
  • ,
  • Momoko Ise
  • ,
  • Akihiro Shiotani
  • ,
  • Eiji Yumoto
  • ,
  • Ryosei Minoda

3
開始ページ
16055
終了ページ
16055
記述言語
英語
掲載種別
DOI
10.1038/mtm.2016.55

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.

リンク情報
DOI
https://doi.org/10.1038/mtm.2016.55
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27579336
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988354

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