Inner ear therapy with protein transduction using polyarginine

• Project/Area Number: 24791788
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Kumamoto University
• Principal Investigator: TAKAMURA Makoto 熊本大学, 医学部附属病院, 医員 (60623973)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Polyarginine / protein / inner ear / ポリアルギニン / 正円窓 / モルモット / 内耳 / protein transduction

Outline of Final Research Achievements

Cell-penetrating peptides (CPPs) are short sequences of amino acids that facilitate the penetration of conjugated cargos across mammalian cell membranes. We showed 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 or vestibular function. A second application 24 h 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’ attached 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 in the cochleae.

Research Products

• [Presentation] Protein Transduction Capabilities using Cell Penetrating Peptides into the Inner ear Protein transduction capabilities using cell penetrating peptides into the inner ear via the round window (2015)
  • Author(s): 竹田 大樹
  • Organizer: Association for Reseach in Otolarynglogy
  • Place of Presentation: Baltimore, Maryland
  • Year and Date: 2015-02-23
• [Presentation] Protein transducing capabilities of arginine-rich cell penetrating peptides ; round window approach (2014)
  • Author(s): 竹田 大樹
  • Organizer: Inner Ear Biology Workshop 2014 in Kyoto
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2014-11-04
• [Presentation] タンパク質導入効率の検討-スポンゼルを用いた正円窓経由での内耳内投与- (2014)
  • Author(s): 竹田 大樹
  • Organizer: 日本耳科学会
  • Place of Presentation: 朱鷺メッセ
  • Year and Date: 2014-10-17
• [Presentation] 正円窓アプローチによるポリアルギニンを用いたタンパク質導入効率の検討 (2014)
  • Author(s): 竹田 大樹
  • Organizer: 第115回日本耳鼻咽喉科学会
  • Place of Presentation: ヒルトン福岡シーホーク
  • Year and Date: 2014-05-16
• [Presentation] Arginine-Rich Cell-Penetrating Peptides（CPPs）を用いた (2013)
  • Author(s): 竹田 大樹
  • Organizer: 耳科学会
  • Place of Presentation: 宮崎
• [Presentation] Inner ear protein transduction utilizing arginine-rich cell-penetrating peptides (2012)
  • Author(s): 蓑田涼生
  • Organizer: ＩＥＢ
  • Place of Presentation: Tubingen,Germany