RU2021112980A - Композиции и способы для снижения экспрессии tau - Google Patents
Композиции и способы для снижения экспрессии tau Download PDFInfo
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Claims (22)
1. Олигонуклеотид, содержащий последовательность нуклеотидных оснований, которая по меньшей мере на 90% идентична любой из последовательностей
GTCTGCCTGTGGCTCCACGA (SEQ ID NO: 329 или SEQ ID NO 485),
AGTCACTCTGGTGAATCCAA (SEQ ID NO: 405 или SEQ ID NO: 486),
где С в любой из последовательностей нуклеотидных оснований представляет собой либо цитозин, либо 5-метилцитозин, и где по меньшей мере один нуклеотид этого олигонуклеотида имеет 2’-модификацию.
2. Олигонуклеотид по п. 1, где указанный олигонуклеотид содержит последовательность нуклеотидных оснований, которая по меньшей мере на 95% идентична любой из последовательностей
GTCTGCCTGTGGCTCCACGA (SEQ ID NO: 329 или SEQ ID NO 485),
AGTCACTCTGGTGAATCCAA (SEQ ID NO: 405 или SEQ ID NO: 486).
3. Олигонуклеотид по п. 2, где указанный олигонуклеотид содержит последовательность нуклеотидных оснований, выбранную из группы, состоящей из
GTCTGCCTGTGGCTCCACGA (SEQ ID NO: 329 или SEQ ID NO 485),
AGTCACTCTGGTGAATCCAA (SEQ ID NO: 405 или SEQ ID NO: 486).
4. Олигонуклеотид по любому из пп. 1-3, где межнуклеозидной связью олигонуклеотида является фосфодиэфирная или фосфортиоатная связь.
5. Олигонуклеотид по п. 4, где межнуклеозидной связью олигонуклеотида является фосфортиоатная связь.
6. Олигонуклеотид по любому из пп. 4, 5, где олигонуклеотид содержит по меньшей мере пять смежных 2'-дезоксинуклеозидов, предпочтительно, по меньшей мере семь смежных 2'-дезоксинуклеозидов, более предпочтительно, по меньшей мере десять смежных 2'-дезоксинуклеозидов.
7. Олигонуклеотид по любому из пп. 5, 6, где указанный олигонуклеотид снижает уровень экспрессии белка tau или мРНК под действием активирующей РНКазы Н.
8. Олигонуклеотид по любому из пп. 1-7, где каждый С в любых последовательностях нуклеотидных оснований представляет собой 5-метилцитозин.
9. Олигонуклеотид по любому из пп. 1-8, где 2'-модификация выбрана из группы, состоящей из 2'-фтора, 2'-дезокси-2'-фтора, 2'-О-метила, 2'-О-метоксиэтила (2'-О-МОЕ), 2'-О-аминопропила (2'-О-АP), 2'-О-диметиламиноэтила (2'-О-DMAOE), 2'-О-диметиламинопропила (2'-О-DMAP), 2'-О-диметиламиноэтилоксиэтила (2'-О-DMAEOE) и 2'-О-N-метилацетамидо (2'-О-NMA).
10. Олигонуклеотид по любому из пп. 1-9, где 2'-модификацией является 2'-О-метоксиэтил (2'-О-МОE).
11. Олигонуклеотид по любому из пп. 1-10, где олигонуклеотид обладает способностью снижать уровень экспрессии мРНК или белка tau по меньшей мере на 30% in vitro или по меньшей мере на 30% in vivo.
12. Олигонуклеотид, состоящий из последовательности нуклеотидных оснований, выбранной из группы
GTCTGCCTGTGGCTCCACGA (SEQ ID NO: 329) или
AGTCACTCTGGTGAATCCAA (SEQ ID NO: 405).
13. Композиция, содержащая олигонуклеотид по любому из пп. 1-12 и фармацевтически приемлемый носитель.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562270165P | 2015-12-21 | 2015-12-21 | |
| US62/270,165 | 2015-12-21 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018126545A Division RU2747734C2 (ru) | 2015-12-21 | 2016-12-19 | Композиции и способы для снижения экспрессии tau |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2022120517A Division RU2022120517A (ru) | 2015-12-21 | 2022-07-27 | Композиции и способы для снижения экспрессии tau |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2021112980A true RU2021112980A (ru) | 2021-05-28 |
| RU2021112980A3 RU2021112980A3 (ru) | 2021-12-28 |
| RU2777570C2 RU2777570C2 (ru) | 2022-08-08 |
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