HRP20190825T1 - Regulacija genske ekspresije posredovana nukleazama - Google Patents

Regulacija genske ekspresije posredovana nukleazama Download PDF

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HRP20190825T1
HRP20190825T1 HRP20190825TT HRP20190825T HRP20190825T1 HR P20190825 T1 HRP20190825 T1 HR P20190825T1 HR P20190825T T HRP20190825T T HR P20190825TT HR P20190825 T HRP20190825 T HR P20190825T HR P20190825 T1 HRP20190825 T1 HR P20190825T1
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cell
protein
tale
zinc finger
nuclease
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HRP20190825TT
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Stuart H. Orkin
Andreas Reik
Fyodor Urnov
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Children's Medical Center Corporation
Sangamo Therapeutics, Inc.
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    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]

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Claims (15)

1. Genetski modificirana stanica koja sadrži genomsku modifikaciju nastalu djelovanjem nukleaze sa cinkanim prstićima (ZFN) ili nukleaze sa efektorskom domenom tipa TAL (TALEN), pri čemu je genomska modifikacija unutar bilo koje od nukleaznih cilјnih sekvenci u SEQ ID NO: 4-80, 143-184, 232-251 i 276 endogene sekvence pojačivača BCL11a i, dalje, pri čemu je genomska modifikacija tipa insercije i/ili delecije.
2. Genetski modificirana stanica prema patentnom zahtjevu 1, pri čemu je stanica matična stanica, opcionalno pri čemu je matična stanica hematopoetska matična stanica kao što je CD34+ hematopoetska matična stanica.
3. Genetski modificirana diferencirana stanica koja potječe od matične stanice prema patentnom zahtjevu 2, opcionalno pri čemu je stanica crvena krvna stanica (RBC).
4. Genetski modificirana stanica prema bilo kojem od patentnih zahtjeva od 1 do 3, gdje: (a) nukleaza se uvodi u stanicu kao polinukleotid; i/ili (b) insercija obuhvaća integraciju donorskog polinukleotida koji kodira transgen, opcionalno gdje: (i) ZFN obuhvaća protein sa strukturama cinkanih prstića, protein sa cinkanim prstićima koji se sastoji od 4, 5 ili 6 domena cinkanih prstića koji sadrže područje prepoznavanja heliksa i, dalјe, gdje protein sa cinkanim prstićima sadrži područja prepoznavanja heliksa po redoslijedu prikazanom u jednom redu Tabele 3 ili Tabele 6; ili (ii) TALEN obuhvaća TALE protein, a TALE protein se sastoji od mnoštva TALE ponovaka, gdje svaki ponovak sadrži hipervarijabilno direzidualno područje (RVD), pri čemu su RVD ovih TALE ponovaka prikazani u jednom redu Tabele 1, Tabele 2 ili Tabele 4.
5. Farmaceutski sastav koji sadrži genetski modificiranu stanicu prema bilo kojem od patentnih zahtjeva od 1 do 4.
6. Protein koji vezuje DNK i sadrži protein sa cinkanim prstićima ili efektorski protein tipa TALE (TALE), gdje se (i) protein sa cinkanim prstićima sastoji od 4, 5 ili 6 domena sa cinkanim prstićima koji sadrže područje prepoznavanja heliksa, pri čemu proteini sa cinkanim prstićima sadrže područja prepoznavanja heliksa po redoslijedu prikazanom u jednom redu Tabele 3 ili Tabele 6; i (ii) TALE protein se sastoji od mnoštva TALE ponovaka, gdje svaki ponovak sadrži hipervarijabilno direzidualno područje (RVD), pri čemu su RVD ovih TALE ponovaka prikazani u jednom redu Tabele 1, Tabele 2 ili Tabele 4.
7. Nukleaza koja sadrži protein sa cinkanim prstićima ili TALE protein prema patentnom zahtjevu 6 i domen isjecanja ili poludomen isjecanja koji je divljeg tipa ili genetski konstruiran.
8. Polinukleotid koji kodira jedan ili više proteina prema patentnom zahtjevu 6 ili nukleazu prema patentnom zahtjevu 7.
9. Izolirana stanica koja sadrži jedan ili više proteina prema patentnom zahtjevu 6 ili patentnom zahtjevu 7 ili jedan ili više polinukleotida prema patentnom zahtjevu 8, opcionalno gdje je stanica hematopoetska matična stanica.
10. Komplet koji sadrži najmanje jedno od: i) polinukleotida koji kodira protein prema patentnom zahtjevu 6 ili patentnom zahtjevu 7 ili ii) protein prema patentnom zahtjevu 6 ili patentnom zahtjevu 7.
11. Postupak izmjene ekspresije globinskog gena u stanici in vitro, postupak koji obuhvaća: uvođenje, u stanicu, jednog ili više polinukleotida prema patentnom zahtjevu 8, pod uvjetima koji omogućavaju da se eksprimira jedan ili više proteina i da se izmjeni ekspresija globinskog gena, opcionalno gdje je ekspresija globinskog gena povećana i/ili globinski gen je gen za gama globin ili beta globin.
12. Postupak prema patentnom zahtjevu 11, koji dalje uključuje integraciju donorske sekvence u genom stanice, opcionalno gdje: (a) donorska sekvenca se uvodi u stanicu upotrebom virusnog vektora, kao oligonukleotid ili u okviru plazmida; (b) stanica je izabrana iz grupe koju čine prekursorska stanica crvenih krvnih stanica (RBC) i hematopoetska matična stanica; i/ili (c) donorska sekvenca sadrži transgen pod kontrolom endogenog ili egzogenog promotora.
13. Farmaceutski sastav prema patentnom zahtjevu 5, za upotrebu u postupku liječenja ili prevencije hemoglobinopatije kod pacijenta kome je potrebno povećanje ekspresije globinskog gena, postupka koji se sastoji od primjene farmaceutskog sastava pacijentu, u količini dovolјnoj da se poveća ekspresija globinskog gena kod pacijenta, opcionalno gdje je hemoglobinopatija talasemija ili anemija srpastih stanica kao što je β-talasemija.
14. Postupak prema patentnom zahtjevu 11 ili farmaceutski sastav za upotrebu prema patentnom zahtjevu 13, gdje ekspresija globinskog gena označava nivo proizvedene globinske iRNK ili globinskog proteina.
15. Jedna ili više nukleaza prema patentnom zahtjevu 7 ili nukleinska kiselina koja kodira jednu ili više nukleaza koje se vezuju za cilјnu sekvencu u okviru bilo koje od SEQ ID NO:4-80, 143-184, 232-251 i 276, za upotrebu u liječenju ili prevenciji hemoglobinopatije, pri čemu nukleaza cilјano djeluje na sekvencu pojačivača BCL11A u stanici i pri čemu su jedna ili više nukleaza tipa ZFN ili TALEN.
HRP20190825TT 2013-11-13 2019-05-02 Regulacija genske ekspresije posredovana nukleazama HRP20190825T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201361903823P 2013-11-13 2013-11-13
US201462042075P 2014-08-26 2014-08-26
PCT/US2014/065473 WO2015073683A2 (en) 2013-11-13 2014-11-13 Nuclease-mediated regulation of gene expression
EP14861930.7A EP3068881B1 (en) 2013-11-13 2014-11-13 Nuclease-mediated regulation of gene expression

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HRP20211706TT HRP20211706T1 (hr) 2013-11-13 2014-11-13 Nukleazom posredovana regulacija ekspresije gena
HRP20190825TT HRP20190825T1 (hr) 2013-11-13 2019-05-02 Regulacija genske ekspresije posredovana nukleazama

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EP (3) EP3960856A1 (hr)
CY (1) CY1121630T1 (hr)
DK (2) DK3068881T3 (hr)
ES (2) ES2721936T3 (hr)
HR (2) HRP20211706T1 (hr)
HU (2) HUE044540T2 (hr)
LT (2) LT3492593T (hr)
PL (2) PL3492593T3 (hr)
PT (2) PT3492593T (hr)
RS (2) RS58671B1 (hr)
SI (2) SI3068881T1 (hr)
WO (1) WO2015073683A2 (hr)

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