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RU2011146202A - Мутантные рецепторы и их использование в системе экспрессии индуцибельного гена на основе ядерного рецептора - Google Patents

Мутантные рецепторы и их использование в системе экспрессии индуцибельного гена на основе ядерного рецептора Download PDF

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RU2011146202A
RU2011146202A RU2011146202/10A RU2011146202A RU2011146202A RU 2011146202 A RU2011146202 A RU 2011146202A RU 2011146202/10 A RU2011146202/10 A RU 2011146202/10A RU 2011146202 A RU2011146202 A RU 2011146202A RU 2011146202 A RU2011146202 A RU 2011146202A
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Сабба Редди ПАЛЛИ
Мохан Басаварайи КУМАР
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Интрексон Корпорейшн
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Abstract

1. Система модулирования экспрессии рекомбинантного гена, которая содержит:а) первую кассету экспрессии рекомбинантного гена, способного к экспрессии в клетке-хозяине, содержащую полинуклеотид, кодирующий первый полипептид, который содержит:i) ДНК-связывающий домен, распознающий элемент ответа, ассоциированный с геном, экспрессия которого должна быть модулирована, выбранный из группы, содержащей домен рецептора экдизона, ДНК-связывающий домен GAL4 и ДНК-связывающий домен LexA иii) первый лигансвязывающий домен ядерного рецептора иб) вторую кассету экспрессии рекомбинантного гена, способного к экспрессии в клетке-хозяине, содержащую полинуклеотид, кодирующий второй полипептид, который содержит:i) домен трансактивации, выбранный из группы, содержащей домен трансактивации рецептора экдизона, домен трансактивации VP16, домен трансактивации кислотного активатора В42 и домен трансактивации р 65; иii) второй лигандсвязывающий домен ядерного рецептора, причем один из первого и второго лигандсвязывающих доменов ядерного рецептора является лигандсвязывающим доменом рецептора экдизона, содержащим мутацию, находящуюся в состоянии, эквивалентном или аналогичном, по меньшей мере, аминокислотному остатку 110 SEQ ID NO: 1, обеспечивающему повышение чувствительности указанного лигандсвязывающего домена к диацилгидразиновому или тетрагидрохинолиновому лиганду, а другой из лигансвязывающих доменов ядерного рецептора способен димеризоваться с лигандсвязывающим доменом рецептора экдизона, содержащим указанную мутацию.2. Система модулирования экспрессии рекомбинантного гена по п.1, в которой мутация представляет собой А110Е, A110N,

Claims (12)

1. Система модулирования экспрессии рекомбинантного гена, которая содержит:
а) первую кассету экспрессии рекомбинантного гена, способного к экспрессии в клетке-хозяине, содержащую полинуклеотид, кодирующий первый полипептид, который содержит:
i) ДНК-связывающий домен, распознающий элемент ответа, ассоциированный с геном, экспрессия которого должна быть модулирована, выбранный из группы, содержащей домен рецептора экдизона, ДНК-связывающий домен GAL4 и ДНК-связывающий домен LexA и
ii) первый лигансвязывающий домен ядерного рецептора и
б) вторую кассету экспрессии рекомбинантного гена, способного к экспрессии в клетке-хозяине, содержащую полинуклеотид, кодирующий второй полипептид, который содержит:
i) домен трансактивации, выбранный из группы, содержащей домен трансактивации рецептора экдизона, домен трансактивации VP16, домен трансактивации кислотного активатора В42 и домен трансактивации р 65; и
ii) второй лигандсвязывающий домен ядерного рецептора, причем один из первого и второго лигандсвязывающих доменов ядерного рецептора является лигандсвязывающим доменом рецептора экдизона, содержащим мутацию, находящуюся в состоянии, эквивалентном или аналогичном, по меньшей мере, аминокислотному остатку 110 SEQ ID NO: 1, обеспечивающему повышение чувствительности указанного лигандсвязывающего домена к диацилгидразиновому или тетрагидрохинолиновому лиганду, а другой из лигансвязывающих доменов ядерного рецептора способен димеризоваться с лигандсвязывающим доменом рецептора экдизона, содержащим указанную мутацию.
2. Система модулирования экспрессии рекомбинантного гена по п.1, в которой мутация представляет собой А110Е, A110N, A110P или A110W.
3. Система модулирования экспрессии рекомбинантного гена по п.1, в которой лигандсвязывающий домен рецептора экдизона дополнительно включает мутацию, находящуюся в состоянии, эквивалентном или аналогичном аминокислотному остатку 52 SEQ ID NO: 1.
4. Система модулирования экспрессии рекомбинантного гена по п.3, в которой мутации представляют собой T52V и А110Р.
5. Система модулирования экспрессии рекомбинантного гена по п.1, в которой лигандсвязывающий домен рецептора экдизона дополнительно включает мутацию, находящуюся в состоянии, эквивалентном или аналогичном аминокислотному остатку 107 и аминокислотному остатку 127 SEQ ID NO: 1.
6. Система модулирования экспрессии рекомбинантного гена по п.5, в которой мутации представляют собой V107I, Y127E и А110Р.
7. Система модулирования экспрессии рекомбинантного гена по п.1, в которой лигандсвязывающий домен рецептора экдизона дополнительно включает мутацию, находящуюся в состоянии, эквивалентном или аналогичном аминокислотному остатку 128 SEQ ID NO: 1.
8. Система модулирования экспрессии рекомбинантного гена по п.7, в которой мутации представляют собой V128F и А110Р.
9. Вектор экспрессии или векторы, содержащий систему модулирования экспрессии рекомбинантного гена по п.1.
10. Клетка-хозяин, содержащая вектор экспрессии или векторы по п.9.
11. Система модулирования экспрессии рекомбинантного гена по п.1, в которой другой лигансвязывающий домен ядерного рецептора является ретиноидным Х-рецептором лигансвязывающего домена.
12. Система модулирования экспрессии рекомбинантного гена по п.11, в которой ретиноидный Х-рецептор лигансвязывающего домена является химерным.
RU2011146202/10A 2004-04-30 2005-05-02 Мутантные рецепторы и их использование в системе экспрессии индуцибельного гена на основе ядерного рецептора RU2539036C2 (ru)

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