DK2836226T3 - Sammensætninger og fremgangsmåder til behandling af hæmoglobinopatier - Google Patents
Sammensætninger og fremgangsmåder til behandling af hæmoglobinopatier Download PDFInfo
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- DK2836226T3 DK2836226T3 DK13751886.6T DK13751886T DK2836226T3 DK 2836226 T3 DK2836226 T3 DK 2836226T3 DK 13751886 T DK13751886 T DK 13751886T DK 2836226 T3 DK2836226 T3 DK 2836226T3
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Claims (10)
1. Isoleret polynukleotid, der koder for en homing-endonuklease (HE), hvor endonukleasen binder til en nukleotidsekvens udvalgt fra gruppen bestående af en Bel Ha-kodende region, en Bel 11a-gen-regulerende region, en føtalt hæmoglobin (HbF)-silencing-region og en Bel Ha-reguleret HbF-silencing-region.
2. Isoleret polynukleotid ifølge krav 1, hvor endonukleasen er: a) en HE, der binder til den Bel Ha-kodende region eller den Bel 11a-gen-regulerende region; eller b) en HE, der kan binde specifikt til en føtalt hæmoglobin (HbF)-silencing-region; eventuelt hvor HE'en er udvalgt fra gruppen bestående af en l-Onul homing-endonuklease, en l-HjeMI homing-endonuklease og en l-CpaMI homing-endonuklease.
3. Isoleret polynukleotid ifølge krav 1 eller 2, hvor endonukleasen er en I-Onul homing-endonuklease, såsom hvor l-Onul homing-endonukleasen omfatter aminosyresekvensen, der kodes af en variant af nukleotidsekvensenen SEQ ID NO: 34, der koder for en l-Onul homing-endonuklease, der kan binde specifikt til føtalt hæmoglobin (HbF) silencing-regionen; eventuelt hvor l-Onul homing-endonukleasen omfatter en eller flere aminosy-resubstitutioner inden for aminosyresekvensen, der kodes af nukleotidsekvensenen SEQ ID NO: 34, hvor hver af aminosyresubstitutionerne er udvalgt fra gruppen bestående af L26, R28, R30, N32, S40, E42, G44, Q46, A70, S72, S78, K80 og T82; eller eventuelt hvor l-Onul homing-endonukleasen omfatter en eller flere aminosy-resubstitutioner inden for aminosyresekvensen, der kodes af nukleotidsekvensenen SEQ ID NO: 34, hvor aminosyresubstitutionen er udvalgt fra gruppen bestående af F182, N184, 1186, S190, K191, Q197, V199, S201, K225, K227, D236, V238 og T240.
4. Isoleret polynukleotid ifølge et hvilket som helst af kravene 1-3, yderligere omfattende et polynukleotid, der koder for et TAL effector (TALE)-DNA- bindende domæne og/eller en TREX2-nuklease, såsom hvor polynukleotiden, der koder for HE-endonukleasen er fusioneret på et polynukleotid, der koder for det TAL effector (TALE)-DNA-bindende domæne eller en TREX2-nuklease.
5. Vektorsystem omfattende en vektor og en polynukleotid ifølge et hvilket som helst af kravene 1 til 4.
6. Vektorsystem ifølge krav 5, hvor vektoren er udvalgt fra gruppen bestående af en AAV6, en modificeret adenovirus-vektor, en integrationsdeficient lentivirus-vektor (IDLV) og en integrationsdeficient foamyvirus-vektor (IDFV).
7. Isoleret homing-endonuklease (HE), der kodes af en polynukleotid ifølge et hvilket som helst af kravene 1 til 4.
8. Sammensætning til anvendelse ved behandling af en hæmoglobinopati, omfattende: a) en polynukleotid ifølge et hvilket som helst af kravene 1 til 4; b) et vektorsystem ifølge krav 5 eller krav 6; eller c) en HE-endonuklease ifølge krav 7.
9. Celle omfattende en polynukleotid ifølge et hvilket som helst af kravene 1 til 4, et vektorsystem ifølge krav 5 eller krav 6 eller en endonuklease ifølge krav 7.
10. Celle ifølge krav 9, hvor cellen er: a) en stamcelle; b) en stamcelle udvalgt fra gruppen bestående af en hæmatopoietisk stamcelle (HSC), en induceret pluripotent stamcelle (iPSC), en embryonisk stamcelle (ES) og en erythroid progenitorcelle; eller c) en stamcelle udvalgt fra gruppen bestående af en hæmatopoietisk stamcelle (HSC), en induceret pluripotent stamcelle (iPSC) og erythroid progenitorcelle.
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|---|---|---|---|
| US201261603231P | 2012-02-24 | 2012-02-24 | |
| PCT/US2013/027459 WO2013126794A1 (en) | 2012-02-24 | 2013-02-22 | Compositions and methods for the treatment of hemoglobinopathies |
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| DK13751886.6T DK2836226T3 (da) | 2012-02-24 | 2013-02-22 | Sammensætninger og fremgangsmåder til behandling af hæmoglobinopatier |
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