Methods and compositions for immune cell crispr screens
AssigneesThe General Hospital Corporation, The Broad Institute, Inc.
InventorsMarcela V. Maus, Robert Manguso, Nelson Knudsen
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Abstract
This application discloses in part methods and compositions for mutating immune cells (e.g., CAR-T cells) and determining mutated immune cell cancer killing efficacy in vivo.
Claims32
A composition comprising a plurality of guide RNA (gRNA) polynucleotides, wherein at least 2 gRNA polynucleotides each comprise a homology region that is complementary to a sense strand or an antisense strand of a different gene encoded by a sequence of any one of SEQ ID NOs:
- 1-135 or a variant thereof.
-13. (canceled)
-19. (canceled)
-23. (canceled)
A composition, comprising a plurality of gRNA polynucleotides comprising the sequences of SEQ ID NOs:
- 136-1315.
-30. (canceled)
-54. (canceled)
-59. (canceled)
-73. (canceled)
A guide RNA polynucleotide comprising a sequence of any one of SEQ ID NOs:
- 136-1315.
-121. (canceled)
A CAR vector comprising the sequence of SEQ ID NO:
- 1319.
A plurality of CAR-T cells, wherein at least two CAR-T cells each comprise a gRNA polynucleotide comprising a homology region that is complementary to a strand or an antisense strand of a different gene encoded by a sequence of any one of SEQ ID NOs:
- 1-135 or a variant thereof.
-154. (canceled)
-173. (canceled)
-205. (canceled)
A plurality of CAR natural killer (CAR-NK) cells, wherein at least two CAR-NK cells comprise a gRNA polynucleotide comprising a homology region that is complementary to a sense strand or an antisense strand of a different gene encoded by a sequence of any one of SEQ ID NOs:
- 1-135 or a variant thereof.
-230. (canceled)
-279. (canceled)
A method comprising administering a mutant CAR-T cell library to a human subject, wherein the mutant CAR-T cell library comprises at least 2 CAR-T cells that each comprise a different gRNA polynucleotide comprising a homology region that is complementary to a different gene sequence of any one of SEQ ID NOs:
- 1-135 or a variant thereof.
Dependencies are inferred from the claim text.