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

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

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6 Citations (Scopus)

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.

Original languageEnglish
Number of pages1
JournalMolecular Therapy - Methods and Clinical Development
Volume3
DOIs
Publication statusPublished - Mar 16 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

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. (2016). Protein transduction therapy into cochleae via the round window niche in guinea pigs. Molecular Therapy - Methods and Clinical Development, 3. https://doi.org/10.1038/mtm.2016.55