Compositions and Methods for Immunotherapy
AssigneeIntellia Therapeutics, Inc.
InventorsAmy Melissa Becker, Surbhi Goel, Sarah Beth Hesse, Troy Aaron Luster, Birgit Schultes, Stephanie A. Yazinski, Pooja Vinay
Life of this patent
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Abstract
Compositions and methods for editing, e.g., altering a DNA sequence, within the TRBC1, TRBC2 and/or TRAC genes are provided. Compositions and methods for immunotherapy are provided, for example.
Claims46
A method of altering a DNA sequence within the TRBC1 and/or TRBC2 gene, or reducing the expression of the TRBC1 and/or TRBC2 gene, comprising delivering a composition to a cell, wherein the composition comprises:
- (a) a guide RNA comprising a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1-24;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 1-6;
- or
- (b) a nucleic acid encoding a guide RNA of (a);
- and
- (c) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent.
A method of altering a DNA sequence, comprising delivering a composition to a cell, wherein the composition comprises:
- (a) a guide RNA comprising a sequence chosen from:
- i. a sequence that comprises 15 consecutive nucleotides ±10 nucleotides of a genomic coordinate listed in any of Tables 1 and/or 3 for SEQ ID NOs:
- 1-89 and 179-184;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence from (i);
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from (i);
- (b) a nucleic acid encoding a guide RNA of (a);
- and
- (c) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent.
(canceled)
A method of immunotherapy comprising administering a composition to a subject, an autologous cell thereof, and/or an allogeneic cell, wherein the composition comprises:
- a. a guide RNA comprising a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1-24;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 1-6;
- or
- b. a nucleic acid encoding a guide RNA of (a);
- and
- c. an RNA-guided DNA binding agent or nucleic acid encoding an RNA-guided DNA binding agent.
A method of altering a DNA sequence within the TRAC gene, or reducing the expression of the TRAC gene, comprising delivering a composition to a cell, wherein the composition comprises:
- a. a guide RNA comprising a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 90-113, 185, and 213-218;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90-95;
- or
- b. a nucleic acid encoding a guide RNA of (a);
- and
- c. an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent.
A method of altering a DNA sequence, comprising delivering a composition to a cell, wherein the composition comprises:
- (a) a guide RNA comprising a sequence chosen from:
- i. a sequence that comprises 15 consecutive nucleotides ±10 nucleotides of a genomic coordinate listed in any of Tables 2 and/or 3 for SEQ ID NOs:
- 90-218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence from (i);
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from (i);
- (b) a nucleic acid encoding a guide RNA of (a);
- and
- (c) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent.
(canceled)
A method of immunotherapy comprising administering a composition to a subject, an autologous cell thereof, and/or an allogeneic cell, wherein the composition comprises:
- a. a guide RNA comprising a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 90-113, 185, and 213-218;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90-95;
- or
- b. a nucleic acid encoding a guide RNA of (a.);
- and
- c. an RNA-guided DNA binding agent or nucleic acid encoding an RNA-guided DNA binding agent.
A method of altering a DNA sequence within the TRBC1, TRBC2 and/or TRAC genes, or reducing the expression of the TRBC1, TRBC2 and/or TRAC genes, comprising delivering to a cell a first guide RNA, a second guide RNA and an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent, wherein the first guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1-24;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 1-6, and
- wherein the second guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 90-113, 185, and 213-218;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90-95.
(canceled)
A method of immunotherapy comprising administering a composition to a subject, an autologous cell thereof, or an allogeneic cell, wherein the composition comprises:
- a first guide RNA, a second guide RNA, and an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent, wherein the first guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1-24;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 1-6, and
- wherein the second guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 90-113, 185, and 213-218;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90-95.
A method of expressing a heterologous immunological receptor via in locus insertion at the TRAC locus, comprising delivering to a cell a first guide RNA, a second guide RNA and an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent, wherein the first guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1, 2, 3, 5, 6;
- and
- v. a guide sequence comprising any one of SEQ ID NOs:
- 2, 3, 5, 6, and
- wherein the second guide RNA comprises a sequence chosen from:
- i. a guide sequence selected from SEQ ID NOs:
- 90, 95, 97, 98, 185, 214, 218;
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90, 95, 97, 98, 185, 214, and 218;
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90, 95, 97, 98, 185, 214, and 218;
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 90, 95, 97, 185, and 214;
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90, 95, and 185;
- and
- vi. a guide sequence comprising SEQ ID NO:
- 90 or 214.
13-14. (canceled)
18-20. (canceled)
23-29. (canceled)
(canceled)
A method of in locus insertion of a TCR, optionally a WT1-specific TCR, comprising delivering to a cell (i) a first guide RNA for inserting the TCR that comprises a guide sequence selected from:
- SEQ ID NOs:
- 90, 95, 97, 98, 185, 214, and 218, (ii) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent;
- and (iii) a donor nucleic acid molecule that encodes a TCR, optionally a WT1-specific TCR.
34-35. (canceled)
A composition comprising:
- a. a guide RNA comprising
- i. a guide sequence selected from SEQ ID NOs:
- 1-89;
- or
- ii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 1-89;
- or
- iii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 1-89;
- or
- iv. a guide sequence comprising any one of SEQ ID NOs:
- 1-24;
- or
- v. a guide sequence comprising any one of SEQ ID NOs:
- 1-6;
- or
- vi. a guide sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- or
- vii. at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- or
- viii. a guide sequence that is at least 95% or 90% identical to a sequence selected from SEQ ID NOs:
- 90-178, 185, and 213-218;
- or
- ix. a guide sequence comprising any one of SEQ ID NOs:
- 90-113 and 213-218;
- or
- v. a guide sequence comprising any one of SEQ ID NOs:
- 90-95;
- and
- b. an RNA-guided DNA binding agent or nucleic acid encoding an RNA-guided DNA binding agent.
37-43. (canceled)
45-48. (canceled)
50-53. (canceled)
56-58. (canceled)
60-63. (canceled)
65-99. (canceled)
101-122. (canceled)
(canceled)
126-322. (canceled)
Dependencies are inferred from the claim text.