Tuning expression for immune or cancer therapies
AssigneesThe J. David Gladstone Institutes, A Testamentary Trust Established Under the Will of J. David, The Regents of the University of California
InventorsJennifer M. Umhoefer et al., Alexander Marson, Maya M. Arce
Life of this patent
Estimating the term…
Abstract
Methods to identify modified Treg cells, compositions comprising those cells or gRNAs, and methods of using those cells are provided.
Claims45
An isolated human Treg cell having altered FOXP3 activity as a result of a modification associated with a gRNA having one of SEQ ID NOs:
- 102-379 and 402-424, including, 102-109, 144, 146, 148, 150, 152-155, 160-163, 168-171, 176, 178, 180, 182, 192, 194, 196, 198, 220-223, 236, 238, 240, 242, 252-255, 272-275, 280-283, 288-291, 308-315, 320, 322, 324, 326, 332-336, 338, 340, 342, 344, 346, 348, 350, 364-367 or 376-379, SEQ ID NOs:
- 110-113, 115-125, 127-135, 164-167, 172-175, 188-191, 200, 202-212, 214, 216, 218, 224-235, 248-251, 268-271, 292-295, 300-303, 352-359 or 368-375;
- or SEQ ID NOs:
- 402-413, or a combination thereof.
An isolated human Treg cell having altered FOXP3 activity as a result of a genetic modification in one of RUNX3, CBFB, DNMT1, E2F3, EGR2, EGR3, ETS1, FOXO1, GABPA, GATA3, HIC1, HIF1A, HSF2, FOXN2, IL2RA, IRF2, IRF4, SMAD4, MTF1, NFKB2, YBX1, MAP2K1, PTEN, RELA, SATB1, SRF, STAT5A, STAT5B, TFDP1, TGFBR1, YY1, ZNF143, NR4A3, MBD2, MED14, SETDB1, MED12, IKZF1, CTCF, GMEB1, IKZF3, MTF2, MGA, USP22, ZMYND8, ZBTB32, FOXP1, TAF5L, TBX21, FOXP3, ATXN7L3, VARS2, ZNF574, BCL11B, MED30, TUBB, ZNF740 or MED11.
An isolated human Treg cell having altered FOXP3 activity as a result of a genetic modification in any one of SEQ ID NOs:
- 20-23.
An isolated human Treg having altered FOXP3 activity as a result of a genetic modification in one of RUNX3, CBFB, GATA3, HIC1, HSF2, IL2RA, IRF4, NFKB2, RELA, STAT5A, TGFBR1, MED14, MED12, CTCF, USP22, ZMYND8, FOXP1, TBX21, FOXP3, ATXN7L3, MED30, or MED11.
An isolated human Treg cell having altered FOXP3 activity as a result of a genetic modification in one of EGR2, EGR3, YBX1, PTEN, RELA, SATB1, SRF, MTF2, TUBB, or ZNF740.
A method to prevent, inhibit or treat cancer in a mammal, comprising administering to the mammal a composition having a plurality of human Treg cells modified with one or more of SEQ ID NOs:
- 102-109, 144, 146, 148, 150, 152-155, 160-163, 168-171, 176, 178, 180, 182, 192, 194, 196, 198, 220-223, 236, 238, 240, 242, 252-255, 272-275, 280-283, 288-291, 308-315, 320, 322, 324, 326, 332-336, 338, 340, 342, 344, 346, 348, 350, 364-367 or 376-379 or 408-413.
A method to prevent, inhibit or treat cancer in a mammal, comprising administering to the mammal a composition having a plurality of human Treg cells having a genetic modification in one or more of RUNX3, CBFB, DNMT1, E2F3, EGR2, EGR3, ETS1, FOXO1, GABPA, GATA3, HIC1, HIF1A, HSF2, FOXN2, IL2RA, IRF2, IRF4, SMAD4, MTF1, NFKB2, YBX1, MAP2K1, PTEN, RELA, SATB1, SRF, STAT5A, STAT5B, TFDP1, TGFBR1, YY1, ZNF143, NR4A3, MBD2, MED14, SETDB1, MED12, IKZF1, CTCF, GMEB1, IKZF3, MTF2, MGA, USP22, ZMYND8, ZBTB32, FOXP1, TAF5L, TBX21, FOXP3, ATXN7L3, VARS2, ZNF574, BCL11B, MED30, TUBB, ZNF740 or MED11.
A method to prevent, inhibit or treat cancer in a mammal, comprising administering to the mammal a composition having a plurality of human Treg cells having a genetic modification in one or more of SEQ ID NOs:
- 20 or 21.
-12. (canceled)
A method to prevent, inhibit or treat an autoimmune disease in a mammal, comprising administering to the mammal a composition having a plurality of Treg cells modified with one of SEQ ID NOs:
- 110-113, 115-125, 127-135, 164-167, 172-175, 188-191, 200, 202-212, 214, 216, 218, 224-235, 248-251, 268-271, 292-295, 300-303, 352-359 or 368-375 or 402-407.
A method to prevent, inhibit or treat an autoimmune disease in a mammal, comprising administering to the mammal a composition having a plurality of Treg cells with a genetic modification in RUNX3, CBFB, DNMT1, E2F3, EGR2, EGR3, ETS1, FOX01, GABPA, GATA3, HIC1, HIF1A, HSF2, FOXN2, IL2RA, IRF2, IRF4, SMAD4, MTF1, NFKB2, YBX1, MAP2K1, PTEN, RELA, SATB1, SRF, STAT5A, STAT5B, TFDP1, TGFBR1, YY1, ZNF143, NR4A3, MBD2, MED14, SETDB1, MED12, IKZF1, CTCF, GMEB1, IKZF3, MTF2, MGA, USP22, ZMYND8, ZBTB32, FOXP1, TAF5L, TBX21, FOXP3, ATXN7L3, VARS2, ZNF574, BCL11B, MED30, TUBB, ZNF740 or MED11.
A method to prevent, inhibit or treat an autoimmune disease in a mammal, comprising administering to the mammal a composition having a plurality of Treg cells having a genetic modification in one of SEQ ID NOs:
- 7-14.
-22. (canceled)
A method to identify regulators of Treg cells, comprising:
- contacting human Treg cells with one or more gRNAs targeted to one or more coding or non-coding regions in one or more genes and a polypeptide comprising a Cas polypeptide or nucleic acid encoding the polypeptide;
- and
- selecting one or more human Treg cells that have an altered activity and optionally isolating the Treg cells with altered activity.
An isolated nucleic acid comprising one of SEQ ID NOs:
- 402-424 or a combination thereof.
A vector comprising at least one of SEQ ID NOs:
- 402-424.
A complex comprising a Cas polypeptide and one of SEQ ID NOs:
- 402-424.
Dependencies are inferred from the claim text.