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RU2006109547A - Способный к интерференции дуплекс рнк, имеющий "тупые" концы и 3, -модификации - Google Patents

Способный к интерференции дуплекс рнк, имеющий "тупые" концы и 3, -модификации Download PDF

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RU2006109547A
RU2006109547A RU2006109547/13A RU2006109547A RU2006109547A RU 2006109547 A RU2006109547 A RU 2006109547A RU 2006109547/13 A RU2006109547/13 A RU 2006109547/13A RU 2006109547 A RU2006109547 A RU 2006109547A RU 2006109547 A RU2006109547 A RU 2006109547A
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double
stranded rna
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alkylaryl
arylalkyl
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Ян ВАЙЛЕР (DE)
Ян Вайлер
Джонатан ХОЛЛ (CH)
Джонатан Холл
Жан-Шарль БОЛОНЬЯ (CH)
Жан-Шарль БОЛОНЬЯ
Франсуа Жан-Шарль НАТТ (CH)
Франсуа Жан-Шарль НАТТ
Роберт ХЭНЕР (CH)
Роберт ХЭНЕР
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Новартис АГ (CH)
Новартис Аг
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Claims (13)

1. Двухцепочечная РНК по меньшей мере с одним «тупым» концом, имеющая по меньшей мере один 3'-конец формулы
Figure 00000001
в которой Х обозначает О или S
R1 и R2 независимо друг от друга обозначают ОН, NH2, SH, алкил, арил, алкиларил, арилалкил, где алкил, арил, алкиларил, арилалкил могут быть замещены дополнительными гетероатомами и функциональными группами, предпочтительно гетероатомом, выбранным из группы, включающей N, О и S, или функциональной группой, выбранной из ОН, NH2, SH, карбоновой кислоты и сложного эфира;
или R1 и R2 могут иметь формулу Y-Z, в которой Y обозначает О, N, S и Z обозначает Н, алкил, арил, алкиларил, арилалкил, где алкил, арил, алкиларил, арилалкил могут быть замещены дополнительными гетероатомами, предпочтительно гетероатомом, выбранным из группы, включающей N, О и S; и где эта двухцепочечная РНК опосредует интерференцию РНК.
2. Двухцепочечная РНК по п.1, в которой R1 обозначает ОН.
3. Двухцепочечная РНК по п.1, которая содержит состоящую из 15-30 нуклеотидов область, комплементарную гену-мишени.
4. Двухцепочечная РНК по п.1, в которой R1 и R2 независимо друг от друга обозначают ОН, NH2, SH, (низш.)алкил, (низш.)арил, (низш.)алкиларил, (низш.)арилалкил, где (низш.)алкил, (низш.)арил, (низш.)алкиларил, (низш.)арилалкил могут быть замещены дополнительными гетероатомами и функциональными группами, предпочтительно гетероатомом, выбранным из группы, включающей N, О и S, или функциональной группой, выбранной из группы, включающей ОН, NH2, SH, карбоновую кислоту и сложный эфир; или R1 и R2 могут иметь формулу Y-Z, в которой Y обозначает О, N, S и Z обозначает, арил, алкиларил, арилалкил, где алкил, арил, алкиларил, арилалкил могут быть замещены дополнительными гетероатомами, предпочтительно гетероатомом, выбранным из группы, включающей N, О и S, при условии, что R1 и R2 оба не обозначают ОН.
5. Двухцепочечная РНК по п.1, в которой R1 обозначает ОН и R2 содержит от 1 до 24 С-атомов.
6. Двухцепочечная РНК по п.1, где РНК имеет два «тупых» конца.
7. Двухцепочечная РНК по п.1, в которой Z обозначает один или несколько нуклеозидов, лишенных азотистого основания.
8. Способ ингибирования гена-мишени, заключающийся в том, что в клетку интродуцируют dsРНК по одному из пп.1-6.
9. Способ по п.8, в котором ген-мишень представляет собой ассоциированный с патогеном ген, вирусный ген или онкоген.
10. Набор, содержащий реагенты для ингибирования экспрессии гена-мишени в клетке, где набор содержит dsРНК по одному из пп.1-6 в клетке и средство для интродукции dsРНК в клетку в количестве, достаточном для ингибирования экспрессии гена-мишени.
11. Фармацевтическая композиция, содержащая эффективное для ингибирования гена-мишени количество по меньшей мере одной dsРНК по одному из пп.1-6.
12. Способ идентификации и/или получения характеристик фармакологических агентов, которые оказывают воздействие по меньшей мере на один белок-мишень, заключающийся в том, что эукариотическую клетку, которая обладает способностью экспрессировать по меньшей мере один эндогенный ген, кодирующий представляющий(ие) интерес белок(ки), приводят в контакт с
(а) по меньшей мере одной молекулой dsРНК по п.1, которая обладает способностью ингибировать экспрессию гена(ов), кодирующего(их) представляющий(ие) интерес белок(ки), и
(б) тестируемой субстанцией или набором тестируемых субстанций, где фармакологические свойства тестируемой субстанции или набора должны быть идентифицированы и/или охарактеризованы.
13. Применение двухцепочечной РНК по пп.1-6 для ингибирования гена-мишени.
RU2006109547/13A 2003-08-28 2004-08-27 Способный к интерференции дуплекс рнк, имеющий "тупые" концы и 3'-модификации RU2399671C2 (ru)

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