Compositions and methods for treating alpha-1 antitrypsin deficiency
AssigneeIntellia Therapeutics, Inc.
InventorsJohn Finn, Hon-Ren Huang, Anthony Forget, Xin Xie
Life of this patent
Estimating the term…
Abstract
Compositions and methods for expressing alpha 1 antitrypsin (AAT) in a host cell are provided. Also provided are compositions and methods for treating subjects having alpha 1 antitrypsin deficiency (AATD).
Claims43
(canceled)
A method of expressing AAT in a subject in need thereof, comprising administering:
- i) a nucleic acid construct comprising a heterologous AAT protein coding sequence;
- ii) a RNA-guided DNA binding agent;
- and
- iii) an albumin guide RNA (gRNA) comprising a sequence chosen from:
- a) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID Nos:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- b) a sequence that is at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- c) a sequence selected from the group consisting of SEQ ID NOs:
- 34, 40, 45, 51, 60, 61, 63, 64, 65, 66, 72, 77, 83, 92, 93, 95, 96, and 97;
- d) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- e) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- f) a sequence selected from the group consisting of SEQ ID NOs:
- 34-97;
- and
- g) a sequence that is complementary to 15 consecutive nucleotides +/−10 nucleotides of the genomic coordinates listed for SEQ ID NOs:
- 2-33,
- thereby expressing AAT in a subject in need thereof.
A method of treating alpha-1 antitrypsin deficiency (AATD) in a subject in need of AAT protein, comprising administering:
- i) a nucleic acid construct comprising a heterologous AAT protein coding sequence;
- ii) a RNA-guided DNA binding agent;
- and
- iii) an albumin guide RNA (gRNA) comprising a sequence chosen from:
- a) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID Nos:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- b) a sequence that is at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- c) a sequence selected from the group consisting of SEQ ID NOs:
- 34, 40, 45, 51, 60, 61, 63, 64, 65, 66, 72, 77, 83, 92, 93, 95, 96, and 97;
- d) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- e) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- f) a sequence selected from the group consisting of SEQ ID NOs:
- 34-97;
- and
- g) a sequence that is complementary to 15 consecutive nucleotides +/−10 nucleotides of the genomic coordinates listed for SEQ ID NOs:
- 2-33,
- thereby treating AATD in the subject.
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22-26. (canceled)
29-31. (canceled)
33-34. (canceled)
The method of claim or 37, wherein the level of AAT is measured in serum, plasma, blood, cerebral spinal fluid, and/or sputum.
39-44. (canceled)
46-49. (canceled)
51-88. (canceled)
A method of treating alpha-1 antitrypsin deficiency (AATD) in a subject in need of AAT protein, comprising administering:
- i) a gene editing system capable of reducing the endogenous expression of SERPINA1;
- ii) a nucleic acid construct comprising a heterologous AAT protein coding sequence;
- iii) a RNA-guided DNA binding agent;
- and
- iv) an albumin guide RNA (gRNA) comprising a sequence chosen from:
- a) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID Nos:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- b) a sequence that is at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2, 8, 13, 19, 28, 29, 31, 32, and 33;
- c) a sequence selected from the group consisting of SEQ ID NOs:
- 34, 40, 45, 51, 60, 61, 63, 64, 65, 66, 72, 77, 83, 92, 93, 95, 96, and 97;
- d) a sequence that is at least 95%, 90%, 85%, 80%, or 75% identical to a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- e) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOs:
- 2-33;
- f) a sequence selected from the group consisting of SEQ ID NOs:
- 34-97;
- and
- g) a sequence that is complementary to 15 consecutive nucleotides +/−10 nucleotides of the genomic coordinates listed for SEQ ID NOs:
- 2-33,
- thereby treating AATD in the subject.
A bidirectional nucleic acid construct comprising:
- a) a first segment comprising a coding sequence for a AAT polypeptide;
- and
- b) a second segment comprising a reverse complement of a coding sequence of the AAT polypeptide,
- wherein the construct does not comprise a promoter that drives the expression of the AAT polypeptide.
92-122. (canceled)
Dependencies are inferred from the claim text.