JP2016198104A - 眼の状態の治療および/または予防のための方法および組成物におけるsiRNAおよびそれらの使用 - Google Patents
眼の状態の治療および/または予防のための方法および組成物におけるsiRNAおよびそれらの使用 Download PDFInfo
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Abstract
【解決手段】TRPV1の発現および/または活性の増加により特徴付けられる眼の状態の治療において使用するためのsiRNAであって、前記分子が、TRPV1の転写物の変異体全てに共通の標的配列(5'-AAGCGCATCTTCTACTTCA-3')を特異的に標的とするsiRNAの提供。
【選択図】なし
Description
in vitro解析
TRPV1の発現を停止させるsiRNA(これは、遺伝子発現の重要な阻害をもたらす)にとって特に有効な標的配列を見出すために、6つの異なるsiRNAを試験した。これらのsiRNAを、配列番号2、配列番号7、および配列番号17〜20として記載する。
センス:5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス:5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号17
センス:5'-CGCAUCUUCUACUUCAACU-3'
アンチセンス:5'-AGUUGAAGUAGAAGAUGCG-3'
配列番号18
センス: 5'-GCGCAUCUUCUACUUCAAC-3'
アンチセンス: 5'-GUUGAAGUAGAAGAUGCGC-3'
配列番号19
センス: 5'-AAAGCCAUGCUCAACCUGC-3'
アンチセンス: 5'-GCAGGUUGAGCAUGGCUUU-3'
配列番号20
センス: 5'-UGAUCGCAGGAGUAUCUUUdTdT-3'
アンチセンス: 5'-AAAGAUACUCCUGCGAUCAdTdT-3'
配列番号3,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号4,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5-UGAAGUAGAAGAUGCGCUU-3'
配列番号8,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号9,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号10,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号11,
センス: 5'-AAGCGCAUCUUCUACUUCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列中、下線は、2'-Oメチル基を含む塩基を示す。
配列番号5,
センス: 5'-AAGCGCAdTCdTdTCdTACdTdTCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号6,
センス: 5'-AAGCGCAdTCdTdTCdTACdTdTCA-3'
アンチセンス: 5'-dTGAAGdTAGAAGAdTGCGCdTdT-3'
配列番号12,
センス: 5'-AAGCGCAdTCUdTCdTACdTdTCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号13,
センス: 5'-AAGCGCAdTCUdTCdTACUdTCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号14,
センス: 5'-AAGCGCAdTCUUCdTACUdTCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号15,
センス: 5'-AAGCGCAdTCUUCUACUdTCA-3'
アンチセンス: 5'-UGAAGUAGAAGAUGCGCUU-3'
配列番号16,
センス: 5'-AAGCGCAdTCUUCUACUdTCA-3'
アンチセンス: 5'-UGAAGdTAGAAGAdTGCGCUU-3'
配列中、一部または全部のウラシルヌクレオチドが、デオキシチミジンヌクレオチドで置換されている。
乾燥眼および眼痛の動物モデルは、ウサギを活用することが多く、この場合は、New Zealand Whiteウサギを活用する。この目的のための本発明のsiRNAのさらなる利点は、標的配列、すなわち、配列番号1は、TRPV1遺伝子の、異なる動物の配列全体を通して高度に保存された領域であることである。実際に、この配列は、ヒトとウサギとの間で同一であり、この動物モデルを、前記疾患の研究にとりわけ適したものにする。
Claims (15)
- TRPV1の発現および/または活性の増加により特徴付けられる眼の状態の治療において使用するためのsiRNAであって、前記分子が、配列番号1を特異的に標的とするsiRNA。
- 前記眼の状態が眼痛である、請求項1に記載のsiRNA。
- 前記眼の状態が、屈折矯正手術に続く感受性の変化、コンタクトレンズの使用、眼球乾燥症候群、およびシェーグレン症候群から選択される、請求項1または2に記載のsiRNA。
- 19ヌクレオチドの二本鎖構造を含む、請求項1から3のいずれか一項に記載のsiRNA。
- 平滑末端である、請求項4に記載のsiRNA。
- 配列番号1を特異的に標的とし、細胞中に導入されるとTRPV1遺伝子の発現を低下させ、19ヌクレオチドの平滑末端の二本鎖構造を含むsiRNA分子。
- 前記siRNAが配列番号2である、請求項1から6のいずれか一項に記載のsiRNA分子。
- 少なくとも1つのヌクレオチドが化学的改変を含む、請求項1から7のいずれか一項に記載のsiRNA分子。
- ヌクレオチドの前記化学的改変が、2'-Oメチル化およびウラシルリボースヌクレオチドのデオキシチミジンヌクレオチドによる置換、ならびにそれらの組合せから選択される、請求項8に記載のsiRNA分子。
- 前記化学的改変が、センス鎖、アンチセンス鎖、または両方の上にある、請求項8または9に記載のsiRNA分子。
- 前記siRNAが、配列番号3〜配列番号6、および配列番号8〜配列番号16から選択される、請求項8から10のいずれかに記載のsiRNA分子。
- TRPV1の発現および/または活性の増加により特徴付けられる眼の状態を治療するための医薬の製造における、請求項1から11のいずれかに記載のsiRNAの使用。
- 前記眼の状態が眼痛である、請求項12に記載の使用。
- 前記眼の状態が、屈折矯正手術に続く感受性の変化、コンタクトレンズの使用、眼球乾燥症候群、およびシェーグレン症候群から選択される、請求項12または13に記載の使用。
- 請求項6から11に記載のsiRNAを少なくとも含む医薬組成物。
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EP10380074A EP2390327A1 (en) | 2010-05-27 | 2010-05-27 | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
EP10380074.4 | 2010-05-27 |
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JP2013511743A Division JP6008845B2 (ja) | 2010-05-27 | 2011-05-27 | 眼の状態の治療および/または予防のための方法および組成物におけるsiRNAおよびそれらの使用 |
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JP2016126328A Pending JP2016198104A (ja) | 2010-05-27 | 2016-06-27 | 眼の状態の治療および/または予防のための方法および組成物におけるsiRNAおよびそれらの使用 |
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US (1) | US9018183B2 (ja) |
EP (2) | EP2390327A1 (ja) |
JP (2) | JP6008845B2 (ja) |
KR (1) | KR101585036B1 (ja) |
CN (1) | CN102918157B (ja) |
AU (1) | AU2011256978B2 (ja) |
CA (1) | CA2800412C (ja) |
CY (1) | CY1121787T1 (ja) |
DK (1) | DK2576782T3 (ja) |
ES (1) | ES2732351T3 (ja) |
HR (1) | HRP20191144T1 (ja) |
HU (1) | HUE044715T2 (ja) |
LT (1) | LT2576782T (ja) |
MX (1) | MX2012012501A (ja) |
PL (1) | PL2576782T3 (ja) |
PT (1) | PT2576782T (ja) |
RS (1) | RS58912B1 (ja) |
SI (1) | SI2576782T1 (ja) |
TR (1) | TR201909158T4 (ja) |
WO (1) | WO2011148193A1 (ja) |
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KR102554783B1 (ko) | 2011-06-30 | 2023-07-11 | 애로우헤드 파마슈티컬스 인코포레이티드 | B형 간염 바이러스의 유전자 발현 저해용 조성물 및 방법 |
GB201215857D0 (en) | 2012-09-05 | 2012-10-24 | Sylentis Sau | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
EP2986599A1 (en) | 2013-04-17 | 2016-02-24 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
EP2865757A1 (en) | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the PDK1 gene. |
EP2865756A1 (en) * | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the FLAP gene. |
US10130651B2 (en) | 2015-08-07 | 2018-11-20 | Arrowhead Pharmaceuticals, Inc. | RNAi Therapy for Hepatitis B Virus Infection |
MA44908A (fr) * | 2015-09-08 | 2018-07-18 | Sylentis Sau | Molécules d'arnsi et leur utilisation dans des procédés et des compositions pour inhiber l'expression du gène nrarp |
JOP20170161A1 (ar) | 2016-08-04 | 2019-01-30 | Arrowhead Pharmaceuticals Inc | عوامل RNAi للعدوى بفيروس التهاب الكبد ب |
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Also Published As
Publication number | Publication date |
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TR201909158T4 (tr) | 2019-07-22 |
EP2390327A1 (en) | 2011-11-30 |
CN102918157A (zh) | 2013-02-06 |
SI2576782T1 (sl) | 2019-08-30 |
JP2013528382A (ja) | 2013-07-11 |
CA2800412A1 (en) | 2011-12-01 |
EP2576782B1 (en) | 2019-03-27 |
EP2576782A1 (en) | 2013-04-10 |
PL2576782T3 (pl) | 2019-09-30 |
CY1121787T1 (el) | 2020-07-31 |
US9018183B2 (en) | 2015-04-28 |
JP6008845B2 (ja) | 2016-10-19 |
HRP20191144T1 (hr) | 2019-10-04 |
DK2576782T3 (da) | 2019-07-01 |
US20130079389A1 (en) | 2013-03-28 |
HUE044715T2 (hu) | 2019-11-28 |
CA2800412C (en) | 2019-09-17 |
WO2011148193A1 (en) | 2011-12-01 |
AU2011256978A1 (en) | 2012-11-15 |
ES2732351T3 (es) | 2019-11-22 |
CN102918157B (zh) | 2016-06-29 |
RS58912B1 (sr) | 2019-08-30 |
KR20130043121A (ko) | 2013-04-29 |
AU2011256978B2 (en) | 2015-06-11 |
KR101585036B1 (ko) | 2016-01-13 |
MX2012012501A (es) | 2013-02-26 |
LT2576782T (lt) | 2019-07-10 |
PT2576782T (pt) | 2019-06-28 |
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