JP6232487B2 - 内耳感覚有毛細胞の再生または置換のための組成物および方法 - Google Patents
内耳感覚有毛細胞の再生または置換のための組成物および方法 Download PDFInfo
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Description
本出願は、2010年6月4日に出願された米国仮出願第61/351,623号に基づく利益を主張する。
(実施例)
本研究の目的は、Hes1発現の減少がネオマイシン誘導性細胞死後の有毛細胞数および毛束数の増加をもたらすことを実証することであった。
本研究の目的は、in vivoで外部磁力を用いて、モルモットの正円窓膜(RWM)を横切って、プラスミドDNA-ルシフェラーゼ(pDNA)およびSPIONを含有するPLGAナノ粒子を送達する能力を実証することであった。
本研究の目的は、外植されたモルモット卵形嚢組織に送達されたHes1 siRNAが、ネオマイシンまたは4-HNE誘導性損傷後に新たな有毛細胞(未成熟に見える有毛細胞)の産生を増加させる効果があるかどうかを確認することであった。
本研究の目的は、7テスラMRIスキャンを用いて非侵襲的にPLGA/SPIONナノ粒子を可視化することができるかどうかを決定することであった。
本研究の目的は、本研究に用いられるHes1 siRNA分子がHes1 mRNAレベルを減少させるために有効であることを実証することであった。
本研究の目的は、Hes1 siRNAが、4-HNEによる損傷後の蝸牛における有毛細胞数の増加に有効であるかどうかを決定することであった。
本実験の目的は、Hes1 siRNAを充填したPLGAナノ粒子が、損傷後の有毛細胞数の増加に有効であることを実証することである。
本研究の目的は、トランスフェクション試薬jetSI(MAPK1 siRNA)またはPLGAナノ粒子(MAPK1 siRNA-NP)に補助されたMAPK1を標的とするsiRNAが、ネオマイシンによる損傷後の球形嚢における有毛細胞死の予防に有効であるかどうかを決定することであった。
Claims (10)
- 生分解性ポリマーと、内耳の組織においてHes1遺伝子の発現を減少させるsiRNA分子とを含み、前記生分解性ポリマーと前記siRNA分子とが均質に混合されている、内耳の有毛細胞の再生のためのナノ粒子組成物。
- 以下のもののうちの1つ以上を含む、請求項1に記載のナノ粒子組成物:
(i)配列番号3およびその相補的配列を含むsiRNA分子、
(ii)配列番号4およびその相補的配列を含むsiRNA分子、
(iii)配列番号5およびその相補的配列を含むsiRNA分子、
(iv)配列番号6およびその相補的配列を含むsiRNA分子、
(v)配列番号7およびその相補的配列を含むsiRNA分子、
(vi)配列番号8およびその相補的配列を含むsiRNA分子。 - 以下のもののうちの1つ以上を含む、請求項1に記載のナノ粒子組成物:
(i)配列番号3および配列番号4を含むsiRNA分子、
(ii)配列番号5および配列番号6を含むsiRNA分子、
(iii)配列番号7および配列番号8を含むsiRNA分子。 - 前記siRNA分子が配列番号7および配列番号8を含む、請求項1に記載のナノ粒子組成物。
- 前記生分解性ポリマーがPLGAである、請求項1〜4のいずれか1項に記載のナノ粒子組成物。
- 超常磁性酸化鉄をさらに含む、請求項1〜5のいずれか1項に記載のナノ粒子組成物。
- 500〜1000個のsiRNA分子を含む、請求項1〜6のいずれか1項に記載のナノ粒子組成物。
- 以下のもののうちのいずれか1つまたは両方を含む、請求項1〜7のいずれか1項に記載のナノ粒子組成物:
(i)内耳の組織においてHes5遺伝子の発現を減少させるsiRNA分子、
(ii)内耳の組織においてMAPK1遺伝子の発現を減少させるsiRNA分子。 - 前記Hes5遺伝子の発現を減少させるsiRNA分子は、(i)配列番号9およびその相補的配列、(ii)配列番号10およびその相補的配列、(iii)配列番号11およびその相補的配列、(iv)配列番号12およびその相補的配列、(v)配列番号13およびその相補的配列、(vi)配列番号14およびその相補的配列、または(vii)これらのいずれかの組合せを含む、請求項8に記載のナノ粒子組成物。
- 前記MAPK1遺伝子の発現を減少させるsiRNA分子は、(i)配列番号15およびその相補的配列、(ii)配列番号16およびその相補的配列、または(iii)これらの組合せを含む、請求項8または9に記載のナノ粒子組成物。
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US35162310P | 2010-06-04 | 2010-06-04 | |
US61/351,623 | 2010-06-04 |
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JP2013513346A Division JP6088967B2 (ja) | 2010-06-04 | 2011-06-02 | 内耳感覚有毛細胞の再生または置換のための組成物および方法 |
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JP2017061491A JP2017061491A (ja) | 2017-03-30 |
JP6232487B2 true JP6232487B2 (ja) | 2017-11-15 |
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JP2016214212A Active JP6232487B2 (ja) | 2010-06-04 | 2016-11-01 | 内耳感覚有毛細胞の再生または置換のための組成物および方法 |
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CN103998454A (zh) * | 2011-08-03 | 2014-08-20 | 夸克制药公司 | 用于治疗听力障碍和平衡障碍的双链寡核苷酸化合物 |
WO2013033513A1 (en) | 2011-08-31 | 2013-03-07 | University Of Georgia Research Foundation, Inc. | Apoptosis-targeting nanoparticles |
US9421173B2 (en) | 2011-09-21 | 2016-08-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Nano delivery systems for siRNA |
CN103182088B (zh) * | 2011-12-28 | 2014-12-03 | 上海市第六人民医院 | Plga修饰磁性纳米簇及其制备方法和应用 |
CA2858630A1 (en) * | 2012-01-12 | 2013-07-18 | Quark Pharmaceuticals, Inc. | Combination therapy for treating hearing and balance disorders |
WO2013123298A1 (en) | 2012-02-17 | 2013-08-22 | University Of Georgia Research Foundation, Inc. | Nanoparticles for mitochondrial trafficking of agents |
US10398663B2 (en) | 2014-03-14 | 2019-09-03 | University Of Georgia Research Foundation, Inc. | Mitochondrial delivery of 3-bromopyruvate |
US9512400B2 (en) * | 2014-04-28 | 2016-12-06 | The University Of Kansas | Reprogramming of human whartons jelly cells to produce hair cells |
CN115814097A (zh) * | 2016-06-03 | 2023-03-21 | 霍夫耳科研究所 | 用于内耳感觉毛细胞再生/替换的联合疗法 |
US11331373B2 (en) | 2017-02-10 | 2022-05-17 | St. Jude Children's Research Hospital | Combination therapy for treating disorders of the ear |
US11883491B2 (en) | 2017-05-03 | 2024-01-30 | St. Jude Children's Research Hospital, Inc. | Compositions and methods for prevention and treatment of hearing loss |
AU2018291045A1 (en) * | 2017-06-30 | 2020-02-13 | Otomagnetics, Inc. | Magnetic nanoparticles for targeted delivery |
WO2022020114A2 (en) | 2020-07-10 | 2022-01-27 | Ting Therapeutics Llc | Methods for the prevention and treatment of hearing loss |
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US20040133099A1 (en) | 2002-12-18 | 2004-07-08 | Dyer R. Kent | Otologic nanotechnology |
AU2004215097A1 (en) * | 2003-02-10 | 2004-09-10 | National Institute Of Advanced Industrial Science And Technology | Regulation of gene expression by DNA interference |
US7723311B2 (en) | 2003-06-18 | 2010-05-25 | Nanobiomagnetics, Inc. | Delivery of bioactive substances to target cells |
US8673634B2 (en) * | 2003-11-13 | 2014-03-18 | Massachusetts Eye & Ear Infirmary | Method for the treatment of hearing loss |
CA2566286A1 (en) * | 2004-05-11 | 2005-12-08 | Rnai Co., Ltd. | Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same |
US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
US7741469B2 (en) * | 2006-04-05 | 2010-06-22 | University Of Iowa Research Foundation | Compositions for treating hearing loss and methods of use thereof |
EP2231197A2 (en) | 2007-12-19 | 2010-09-29 | Ramot at Tel-Aviv University Ltd. | Methods of generating expanded and re-differentiated adult islet beta cells for use in the treatment of diabetes |
WO2009104051A2 (en) * | 2007-12-31 | 2009-08-27 | Lu Patrick Y | Combinational therapeutics for treatment of prostate cancer using epoxy encapsulated magnetic particles and rnai medicine |
WO2009147684A2 (en) * | 2008-06-06 | 2009-12-10 | Quark Pharmaceuticals, Inc. | Compositions and methods for treatment of ear disorders |
CA2728176C (en) * | 2008-06-16 | 2017-07-04 | Bind Biosciences, Inc. | Drug loaded polymeric nanoparticles and methods of making and using same |
US8784870B2 (en) * | 2008-07-21 | 2014-07-22 | Otonomy, Inc. | Controlled release compositions for modulating free-radical induced damage and methods of use thereof |
JP4340744B2 (ja) * | 2009-03-17 | 2009-10-07 | 株式会社ホソカワ粉体技術研究所 | 薬剤溶出型ステント |
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JP2013527244A (ja) | 2013-06-27 |
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