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US 2021/0228629 A1Published application
Anti-bcma car-t-cells for plasma cell depletion
AssigneesCrispr Therapeutics AG, Bayer HealthCare LLC
InventorGregory COST
Life of this patent
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Abstract
The present application relates to compositions and methods for controlled plasma cell depletion, such as for the treatment of various diseases and conditions associated with plasma cells.
Claims145
An engineered T cell comprising a) an endogenous T cell receptor alpha (TIM) gene modified to encode a non-functional T cell receptor alpha constant (TRAC) domain;
- and b) a nucleic acid encoding a chimeric antigen receptor (CAR) that can recognize B-cell maturation antigen (BCMA).
A guide RNA (gRNA) comprising a sequence that is complementary to a sequence in an endogenous TRA gene within or near a region encoding the TRAC domain.
A guide RNA (gRNA) comprising a sequence that is complementary to a sequence within or near an endogenous IL2RG gene.
A vector comprising the nucleic acid sequence of any one of SEQ ID NOs:
- 19-46, or a variant thereof having at least 85% homology to any one of SEQ ID NOs:
- 19-46.
A method of editing the genome of a cell, the method comprising providing to the cell a first gRNA, a second gRNA, an RGEN or a nucleic acid encoding the RGEN, a first vector, and a second vector, wherein
- (A) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 1 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 1, the first vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 28, 31, 34, and 37 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 28, 31, 34, and 37, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44 or a variant thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44;
- (B) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 2 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 2, the first vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 29, 32, 35, and 38 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 29, 32, 35, and 38, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44 or a variant thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44;
- or
- (C) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 3 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 3, the first vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 30, 33, 36, and 39 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 30, 33, 36, and 39, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second vector comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44 or a variant thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 40-44.
25 more elements
A method of editing the genome of a cell, the method comprising providing to the cell a first gRNA, a second gRNA, an RGEN or a nucleic acid encoding the RGEN, a first vector, and a second vector, wherein
- (A) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 1 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 1, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 19 or 22 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 19 or 22, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 45 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 45;
- (B) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 2 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 2, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 20 or 23 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 20 or 23, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 45 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 45;
- or
- (C) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 3 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 3, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 21 or 24 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 21 or 24, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 45 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 45.
25 more elements
A method of editing the genome of a cell, the method comprising providing to the cell a first gRNA, a second gRNA, an RGEN or a nucleic acid encoding the RGEN, a first vector, and a second vector, wherein
- (A) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 1 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 1, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 25 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 25, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 46 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 46;
- (B) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 2 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 2, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 26 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 26, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 46 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 46;
- or
- (C) the first gRNA comprises the polynucleotide sequence of SEQ ID NO:
- 3 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 3, the first AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 27 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 27, the second gRNA comprises the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18 and variants thereof having at least 85% homology to the polynucleotide sequence of any one of SEQ ID NOs:
- 4-18, and the second AAV vector comprises the polynucleotide sequence of SEQ ID NO:
- 46 or a variant thereof having at least 85% homology to the polynucleotide sequence of SEQ ID NO:
- 46.
25 more elements
Dependencies are inferred from the claim text.