Protein transduction therapy into cochleae via the round window niche in guinea pigs
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 ind...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S232905011730027X |
| _version_ | 1818994628910645248 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hiroki Takeda |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T21:00:59Z |
| format | Article |
| id | doaj.art-25b6b285174a4456bf9226eba0c78491 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-20T21:00:59Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-25b6b285174a4456bf9226eba0c784912022-12-21T19:26:43ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012016-01-013C10.1038/mtm.2016.55Protein transduction therapy into cochleae via the round window niche in guinea pigsHiroki Takeda0Takaomi Kurioka1Taku Kaitsuka2Kazuhito Tomizawa3Takeshi Matsunobu4Farzana Hakim5Kunio Mizutari6Toru Miwa7Takao Yamada8Momoko Ise9Akihiro Shiotani10Eiji Yumoto11Ryosei Minoda12Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology, National Defense Medical College, Tokorozawa, JapanDepartment of Molecular Physiology, Kumamoto University, Kumamoto, JapanDepartment of Molecular Physiology, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology, National Defense Medical College, Tokorozawa, JapanDepartment of Molecular Physiology, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology, National Defense Medical College, Tokorozawa, JapanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology, National Defense Medical College, Tokorozawa, JapanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University, Kumamoto, JapanCell-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.http://www.sciencedirect.com/science/article/pii/S232905011730027X |
| spellingShingle | 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 Protein transduction therapy into cochleae via the round window niche in guinea pigs Molecular Therapy: Methods & Clinical Development |
| title | Protein transduction therapy into cochleae via the round window niche in guinea pigs |
| title_full | Protein transduction therapy into cochleae via the round window niche in guinea pigs |
| title_fullStr | Protein transduction therapy into cochleae via the round window niche in guinea pigs |
| title_full_unstemmed | Protein transduction therapy into cochleae via the round window niche in guinea pigs |
| title_short | Protein transduction therapy into cochleae via the round window niche in guinea pigs |
| title_sort | protein transduction therapy into cochleae via the round window niche in guinea pigs |
| url | http://www.sciencedirect.com/science/article/pii/S232905011730027X |
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