RU2006144817A - Модуляция wrn-опосредованной теломера-инициированной клеточной передачи сигнала - Google Patents

Модуляция wrn-опосредованной теломера-инициированной клеточной передачи сигнала Download PDF

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RU2006144817A
RU2006144817A RU2006144817/13A RU2006144817A RU2006144817A RU 2006144817 A RU2006144817 A RU 2006144817A RU 2006144817/13 A RU2006144817/13 A RU 2006144817/13A RU 2006144817 A RU2006144817 A RU 2006144817A RU 2006144817 A RU2006144817 A RU 2006144817A
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wrn
cell
modulator
sequence
induction
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Барбара А. ДЖИЛКРЕСТ (US)
Барбара А. Джилкрест
Марк С. ЭЛЛЕР (US)
Марк С. ЭЛЛЕР
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Трастиз Оф Бостон Юниверсити (Us)
Трастиз Оф Бостон Юниверсити
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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Claims (11)

1. Способ скрининга модулятора WRN (мутантного белка при синдроме Вернера), включающий
(а) получение клетки, которая экспрессирует WRN,
(б) контактирование потенциальных модуляторов с указанной клеткой в условиях, в которых модулятор поглощается клеткой, и
(в) оценку свойства клетки, связанного с активацией метаболического пути ответа на повреждение ДНК,
в котором изменение свойства по сравнению с контролем выявляет модулятор WRN.
2. Способ по п.1, в котором указанные потенциальные модуляторы специфически связываются с WRN.
3. Способ по п.1, в котором свойство указанной клетки выбрано из группы, состоящей из клеточной пролиферации, клеточной жизнеспособности, клеточной морфологии, активности SA-β-Gal (связанной со старением β-галактозидазы), фосфорилирования опухолевого репрессора р53, фосфорилирования белка р95 (нибрина), фосфорилирования киназы ATM, фосфорилирования гистона Н2АХ, индукции ареста S-фазы и индукции апоптоза.
4. Способ по одному из пп.1-3, в котором упомянутая клетка является раковой клеткой.
5. Способ по п.4, в котором упомянутые потенциальные модуляторы выбраны из группы, состоящей из углеводов, моносахаридов, олигосахаридов, полисахаридов, аминокислот, пептидов, олигопептидов, полипептидов, белков, нуклеозидов, нуклеотидов, олигонуклеотидов, полинуклеотидов, липидов, ретиноидов, стероидов, гликопептидов, гликопротеинов, протеогликанов и небольших органических молекул.
6. Способ скрининга модулятора WRN, включающий
(а) контактирование WRN с потенциальным модулятором in vitro в присутствии в качестве субстрата для WRN нуклеиновой кислоты и
(б) оценку гидролиза указанного субстрата, в соответствии с которой модулятор идентифицируют по изменению гидролиза указанного субстрата по сравнению с контролем.
7. Способ по п.6, в котором указанный субстрат, представляющий нуклеиновую кислоту, является олигонуклеотидом, у которого, по меньшей мере, 33% последовательности идентично последовательности (TTAGGG)n, в которой n=1-20.
8. Применение композиции, включающей активатор WRN, для получения лекарственного средства для лечения рака, индукции апоптоза, индуцировании клеточного старения, стимуляции таннинга, стимуляции клеточной дифференцировки или стимуляции иммуносупрессии.
9. Применение по п.8, в котором активатором является олигонуклеотидный активатор WRN, у которого, по меньшей мере, 33% нуклеотидной последовательности идентично последовательности (TTAGGG)n и, по меньшей мере, первые x 3'-нуклеотидные связи способны гидролизоваться 3' 5'-нуклеазой, причем n=1-20, a x обозначает примерно от 1 до примерно 10.
10. Композиция, включающая олигонуклеотид, у которого, по меньшей мере, 33% нуклеотидной последовательности идентично последовательности (TTAGGG)n, присутствует, по меньшей мере, одна гидролизуемая межнуклеотидную связь, по меньшей мере, первые x 3'-нуклеотидные связи способны гидролизоваться 3' 5'-нуклеазой, причем n=1-20, а x обозначает примерно от 1 до примерно 10.
11. Композиция по п.10, в которой 3' 5'-нуклеазой является WRN.
RU2006144817/13A 2004-05-19 2005-05-19 Модуляция wrn-опосредованной теломера-инициированной клеточной передачи сигнала RU2006144817A (ru)

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US57262504P 2004-05-19 2004-05-19
US60/572,625 2004-05-19

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US (1) US20080221052A1 (ru)
EP (2) EP2434009A1 (ru)
JP (1) JP2007537758A (ru)
KR (1) KR20070030219A (ru)
CN (2) CN101869575A (ru)
AU (1) AU2005245932A1 (ru)
BR (1) BRPI0511142A (ru)
CA (1) CA2566859C (ru)
HK (1) HK1104062A1 (ru)
IL (1) IL179199A (ru)
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NO (1) NO20065782L (ru)
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Cited By (1)

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Publication number Priority date Publication date Assignee Title
RU2550267C2 (ru) * 2012-12-12 2015-05-10 Елена Андреевна Чирясова Способ воздействия на пролиферативный статус клеток с помощью специфических нуклеотидных последовательностей g-цепи теломерной днк человека

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US20100086941A1 (en) * 2008-10-01 2010-04-08 Adami Guy R Methods for determining aged based accumulation of senescent cells using senescence specific DNA damage markers
US20110052676A1 (en) * 2009-09-01 2011-03-03 James Vincent Gruber Composition For Delaying Cellular Senescence
US11530413B2 (en) 2017-07-21 2022-12-20 Novartis Ag Compositions and methods to treat cancer
US20210371855A1 (en) * 2018-06-15 2021-12-02 Ideaya Biosciences, Inc. Methods of inhibiting proliferative cells

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FR2521565B1 (fr) 1982-02-17 1985-07-05 Dior Sa Parfums Christian Melange pulverulent de constituants lipidiques et de constituants hydrophobes, procede pour le preparer, phases lamellaires lipidiques hydratees et procede de fabrication, compositions pharmaceutiques ou cosmetiques comportant des phases lamellaires lipidiques hydratees
FR2534487B1 (fr) * 1982-10-15 1988-06-10 Dior Christian Parfums Procede d'homogeneisation de dispersions de phases lamellaires lipidiques hydratees, et suspensions obtenues par ce procede
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AU2004233188A1 (en) 2003-04-11 2004-11-04 Trustees Of Boston University Modulation of telomere-initiated cell signaling

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2550267C2 (ru) * 2012-12-12 2015-05-10 Елена Андреевна Чирясова Способ воздействия на пролиферативный статус клеток с помощью специфических нуклеотидных последовательностей g-цепи теломерной днк человека

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CN1965076A (zh) 2007-05-16
TR200606490A2 (tr) 2008-05-21
KR20070030219A (ko) 2007-03-15
EP2434009A1 (en) 2012-03-28
US20080221052A1 (en) 2008-09-11
AU2005245932A1 (en) 2005-12-01
BRPI0511142A (pt) 2007-12-04
CA2566859A1 (en) 2005-12-01
NZ551323A (en) 2010-03-26
CN1965076B (zh) 2011-01-26
EP1761629A2 (en) 2007-03-14
MXPA06013263A (es) 2007-08-14
JP2007537758A (ja) 2007-12-27
NO20065782L (no) 2006-12-18
WO2005113764A2 (en) 2005-12-01
IL179199A0 (en) 2007-03-08
HK1104062A1 (en) 2008-01-04
CA2566859C (en) 2011-07-19
TR200606490T1 (tr) 2007-01-22
IL179199A (en) 2010-12-30
CN101869575A (zh) 2010-10-27

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