RU2013104890A - Вирионоподобные частицы для доставки самореплицирующихся молекул рнк - Google Patents

Вирионоподобные частицы для доставки самореплицирующихся молекул рнк Download PDF

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RU2013104890A
RU2013104890A RU2013104890/15A RU2013104890A RU2013104890A RU 2013104890 A RU2013104890 A RU 2013104890A RU 2013104890/15 A RU2013104890/15 A RU 2013104890/15A RU 2013104890 A RU2013104890 A RU 2013104890A RU 2013104890 A RU2013104890 A RU 2013104890A
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Эндрю ДЖИЛЛ
Кристиан МАНДЛЬ
Дерек О`Хейган
Манмохан Сингх
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Новартис Аг
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Abstract

1. Невирионная частица для доставки in vivo РНК в клетку позвоночного, где (а) частица включает материал доставки, либо (i) который инкапсулирует самореплицирующуюся молекулу РНК, кодирующую иммуноген, либо (ii) на котором адсорбируется самореплицирующаяся молекула РНК, кодирующая иммуноген, и (b) РНК не включает модифицированные нуклеотиды.2. Частица по п.1, где частица представляет собой липосому, и в ней инкапсулирована РНК.3. Частица по п.1, где частица представляет собой нетоксичную и биодеградируемую полимерную микрочастицу, и РНК адсорбирована на ней.4. Частица по п.1, где частица представляет собой биодеградируемую поперечно сшитую наночастицу из олигомерного полимера, образованную путем взаимодействия полимера, поперечно сшивающего агента, заряженного мономера и РНК.5. Частица по п.2, где липосома включает липид с катионной головной группой.6. Частица по п.2 или 5, где липосома включает липид с цвиттерионной головной группой.7. Частица по п.2 или 5, где липосома имеет диаметр в диапазоне 50-220 нм.8. Частица по п.3, где частица включает поли(D,L-лактид-со-гликолид).9. Частица по п.3 или 8, где частица имеет диаметр от 30 нм до 7 мкм.10. Частица по п.1, где самореплицирующаяся молекула РНК кодирует (i) РНК-зависимую РНК-полимеразу, которая может транскрибировать РНК с самореплицирующейся молекулы РНК, и (ii) иммуноген.11. Частица по п.10, где молекула РНК содержит две открытые рамки считывания, первая из которых кодирует репликазу альфа-вируса, а вторая кодирует иммуноген.12. Частица по п.1, где молекула РНК имеет длину 9000-12000 нуклеотидов.13. Частица по п.1, где иммуноген может вызывать иммунный ответ in vivo против бактерии, вируса, грибка или паразита

Claims (19)

1. Невирионная частица для доставки in vivo РНК в клетку позвоночного, где (а) частица включает материал доставки, либо (i) который инкапсулирует самореплицирующуюся молекулу РНК, кодирующую иммуноген, либо (ii) на котором адсорбируется самореплицирующаяся молекула РНК, кодирующая иммуноген, и (b) РНК не включает модифицированные нуклеотиды.
2. Частица по п.1, где частица представляет собой липосому, и в ней инкапсулирована РНК.
3. Частица по п.1, где частица представляет собой нетоксичную и биодеградируемую полимерную микрочастицу, и РНК адсорбирована на ней.
4. Частица по п.1, где частица представляет собой биодеградируемую поперечно сшитую наночастицу из олигомерного полимера, образованную путем взаимодействия полимера, поперечно сшивающего агента, заряженного мономера и РНК.
5. Частица по п.2, где липосома включает липид с катионной головной группой.
6. Частица по п.2 или 5, где липосома включает липид с цвиттерионной головной группой.
7. Частица по п.2 или 5, где липосома имеет диаметр в диапазоне 50-220 нм.
8. Частица по п.3, где частица включает поли(D,L-лактид-со-гликолид).
9. Частица по п.3 или 8, где частица имеет диаметр от 30 нм до 7 мкм.
10. Частица по п.1, где самореплицирующаяся молекула РНК кодирует (i) РНК-зависимую РНК-полимеразу, которая может транскрибировать РНК с самореплицирующейся молекулы РНК, и (ii) иммуноген.
11. Частица по п.10, где молекула РНК содержит две открытые рамки считывания, первая из которых кодирует репликазу альфа-вируса, а вторая кодирует иммуноген.
12. Частица по п.1, где молекула РНК имеет длину 9000-12000 нуклеотидов.
13. Частица по п.1, где иммуноген может вызывать иммунный ответ in vivo против бактерии, вируса, грибка или паразита.
14. Частица по п.13, где иммуноген может вызывать иммунный ответ in vivo против гликопротеина F респираторно-синцитиального вируса.
15. Частица по п.6, где липосома имеет диаметр в диапазоне 50-220 нм.
16. Фармацевтическая композиция, включающая частицу по п.1.
17. Фармацевтическая композиция, включающая частицу по п.2.
18. Фармацевтическая композиция, включающая частицу по п.3.
19. Способ повышения защитного иммунного ответа у позвоночного, включающий стадию введения позвоночному эффективного количества частицы по п.1.
RU2013104890/15A 2010-07-06 2011-07-06 Вирионоподобные частицы для доставки самореплицирующихся молекул рнк RU2013104890A (ru)

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PCT/US2011/043103 WO2012006376A2 (en) 2010-07-06 2011-07-06 Virion-like delivery particles for self-replicating rna molecules

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