RU2003131324A - Улучшенные условно реплицирующие векторы для подавления вирусных инфекций - Google Patents

Улучшенные условно реплицирующие векторы для подавления вирусных инфекций Download PDF

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RU2003131324A
RU2003131324A RU2003131324/13A RU2003131324A RU2003131324A RU 2003131324 A RU2003131324 A RU 2003131324A RU 2003131324/13 A RU2003131324/13 A RU 2003131324/13A RU 2003131324 A RU2003131324 A RU 2003131324A RU 2003131324 A RU2003131324 A RU 2003131324A
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vector
conditionally replicating
cell
helper
specified
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Лоран ЮМО (US)
Лоран ЮМО
Юэксиа ЛИ (US)
Юэксиа ЛИ
Рэндалл МЕРЛИНГ (US)
Рэндалл МЕРЛИНГ
Боро ДРОПУЛИК (US)
Боро ДРОПУЛИК
Кати Л. ШОНЕЛИ (US)
Кати Л. ШОНЕЛИ
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Вирэкссис Корпорейшн (Us)
Вирэкссис Корпорейшн
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Claims (24)

1. Система условно реплицирующийся вектор-хелпер, включающая
условно реплицирующийся вектор, содержащий одну или более последовательностей нуклеиновых кислот, которые уменьшают риск рекомбинации с хелперным вектором, и
хелперный вектор.
2. Система по п.1, отличающаяся тем, что указанная одна или более последовательностей нуклеиновых кислот, которые снижают риск рекомбинации, выбраны из рибозима, который расщепляет хелперный вектор, последовательностей, которые содержат одну или более замен, инсерций или делеций, которые уменьшают вероятность рекомбинации с хелперным вектором, или последовательностей, которые были вырождены, чтобы уменьшить вероятность рекомбинации с хелперным вектором.
3. Система по п.1, отличающаяся тем, что указанный хелперный вектор содержит вырожденные последовательности по отношению к одной или более последовательностям хелперного вектора, чтобы снизить вероятность рекомбинации с указанным условно реплицирующимся вектором, или донорные сайты сплайсинга, так чтобы были удалены последовательности упаковки или RRE, чтобы предотвратить совместную локализацию с указанным условно реплицирующимся вектором.
4. Система по п.1, отличающаяся тем, что указанный вектор содержит ген MGMT.
5. Система по п.1, отличающаяся тем, что указанный хелпер кодирует гетерологичный белок оболочки и/или содержит гетерологичный RRE по сравнению с указанным условно реплицирующимся вектором или гетерологичную последовательность gag по сравнению с указанным вектором.
6. Система по п.5, отличающаяся тем, что указанный гетерологичный белок оболочки находится под Rev-зависимым контролем, и/или указанный гетерологичный белок оболочки выбран из белков оболочки VSV-G, RD114, вируса бешенства, GALV и химерных белков оболочки.
7. Система по п.1, отличающаяся тем, что указанный условно реплицирующийся вектор не кодирует или не экспрессирует вспомогательных вирусных белков.
8. Система по п.1, отличающаяся тем, что указанный условно реплицирующийся вектор получен из ВИЧ-1.
9. Система по п.1, отличающаяся тем, что указанный условно реплицирующийся вектор кодирует укороченный белок CCR5.
10. Система по п.1, отличающаяся тем, что указанный условно реплицирующийся вектор содержит последовательность, которая улучшает трансдукцию указанного вектора.
11. Система по п.1, отличающаяся тем, что указанный вектор кодирует химерный эпитоп CTL ВИЧ.
12. Клетка, содержащая систему по любому из предшествующих пунктов.
13. Способ упаковки условно реплицирующегося вектора, включающий инкубирование клетки по п.12 в условиях, при которых указанный вектор пакуется.
14. Условно реплицирующийся вектор, полученный способом по п.13.
15. Клетка, инфицированная вектором по п.14.
16. Способ селекции клеток по п.15, включающий контактирование указанных клеток с BG или BCNU.
17. Способ по п.16, отличающийся тем, что опухолевые клетки, не инфицированные вектором, погибают.
18. Способ предотвращения или ингибирования продуцирования вирусной ДНК в клетке, инфицированной вирусом, включающий в себя
введение в указанную клетку перед инфицированием клетки указанным вирусом условно реплицирующегося вирусного вектора,
где указанный вектор предотвращает или ингибирует продуцирование вирусной ДНК.
19. Способ по п.18, отличающийся тем, что указанная вирусная ДНК может быть интегрированной в геном клетки.
20. Способ по п.18, отличающийся тем, что указанный вирус является вирусом дикого типа.
21. Способ по п.18, отличающийся тем, что указанной клеткой является клетка CD4+.
22. Способ по любому из пп.18-21, отличающийся тем, что указанным вирусом является ВИЧ-1.
23. Способ по п.18, отличающийся тем, что указанный вектор интегрируется в геном клетки таким же способом, как и способ, который используется указанным вирусом.
24. Способ по п.18, отличающийся тем, что указанный вектор содержит ген, который необходимо экспрессировать, и одну или более начальных нуклеотидных последовательностей, и где вектор:
(a) реплицируется в клетке-хозяине только при комплементации штаммом вируса дикого типа, хелперным вирусом или
хелперным вектором, каждый из которых является чувствительным к присутствию указанной одной или более начальных нуклеотидных последовательностей;
(b) резистентен к присутствию указанной одной или более начальных нуклеотидных последовательностей; и
(c) содержит одну или более замен, инсерций или делеций, которые уменьшают вероятность образования компетентного по репликации вектора.
RU2003131324/13A 2001-03-27 2002-03-26 Улучшенные условно реплицирующие векторы для подавления вирусных инфекций RU2003131324A (ru)

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US09/819,401 US20030026791A1 (en) 2001-03-27 2001-03-27 Conditionally replicating vectors for inhibiting viral infections
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