IP Library › Granted Patent US 12,234,449
Granted Patent B2
US 12,234,449 · App. 17/688,782 · Granted Feb 25, 2025

CRISPR/Cas-related methods and compositions for treating Leber's congenital amaurosis 10 (LCA10)

Inventors: Morgan Lee Maeder (Jamaica Plain, MA); David A. Bumcrot (Belmont, MA); Shen Shen (Watertown, MA)
Assignee: EDITAS MEDICINE, INC.
C12N15/1024C12N9/22C12N15/11C12N15/113C12N15/86C12N2310/10C12N2310/20C12N2750/14132C12N2750/14142C12N2750/14143C12N2750/14145C12N2750/14151
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Quick Facts
Patent No.
US 12,234,449
App. No.
17/688,782
Granted
Feb 25, 2025
Kind
B2
Abstract

CRISPR/CAS-related compositions and methods for treatment of Leber's Congenital Amaurosis 10 (LCA10) are disclosed.

Claims (40)

1. A guide RNA (gRNA) molecule comprising a targeting domain which is complementary with a target domain from the CEP290 gene.

2. The gRNA molecule of claim 1 , wherein said targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence selected from the group consisting of SEQ ID NOs. 304-386, 389-395, 397, 398, 457-591, 594-595, 597-600, 603, 609, 610, 613-638, 642-645, 648-652, 655, 656, 747-2777, and 2780.

3. The gRNA molecule of claim 2 , comprising from 5′ to 3′:

a targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

4. A nucleic acid that comprises: (a) a sequence that encodes a first gRNA molecule comprising a first targeting domain that is complementary with a first target domain in the CEP290 gene.

5. The nucleic acid of claim 4 , wherein said first targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a first targeting domain sequence selected from the group consisting of SEQ ID NOs. 304-386, 389-395, 397, 398, 457-591, 594-595, 597-600, 603, 609, 610, 613-638, 642-645, 648-652, 655, 656, 747-2777, and 2780.

6. The nucleic acid of claim 5 , comprising from 5′ to 3′:

a first targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

7. The nucleic acid of claim 6 , further comprising: (b) a sequence that encodes a Cas9 molecule.

8. The nucleic acid of claim 7 , further comprising: (c) a sequence that encodes a second gRNA molecule having a second targeting domain that is complementary to a second target domain of the CEP290 gene.

9. The nucleic acid of claim 8 , wherein said second gRNA molecule comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a first targeting domain sequence selected from the group consisting of SEQ ID NOs. 304-386, 389-395, 397, 398, 457-591, 594-595, 597-600, 603, 609, 610, 613-638, 642-645, 648-652, 655, 656, 747-2777, and 2780.

10. The nucleic acid of claim 9 , comprising from 5′ to 3′:

a second targeting domain;

a first complementarity domain;

a linking domain;

a second complementarity domain;

a proximal domain; and

a tail domain.

11. The nucleic acid of claim 10 , further comprising a promoter sequence for driving expression of the Cas9, the promoter sequence selected from the group consisting of SEQ ID NOs: 401-403.

12. The nucleic acid of claim 7 , wherein the Cas9 is S. aureus Cas9.

13. The nucleic acid of claim 12 , further comprising

a) a CMV promoter for Cas9,

b) an EFS promoter for Cas9, or

c) hGRK1 promoter for Cas9.

14. A CRISPR/Cas system comprising

a first guide RNA (gRNA) molecule comprising a first targeting domain which is complementary with a first target domain from the CEP290 gene;

a Cas9 molecule, wherein the first gRNA molecule is configured to form a first complex with the Cas9 molecule.

15. The CRISPR/Cas system of claim 14 , wherein said first targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence selected from the group consisting of SEQ ID NOs. 304-386, 389-395, 397, 398, 457-591, 594-595, 597-600, 603, 609, 610, 613-638, 642-645, 648-652, 655, 656, 747-2777, and 2780.

16. The CRISPR/Cas system of claim 15 , further comprising a second gRNA molecule having a second targeting domain that is complementary to a second target domain of the CEP290 gene, wherein the second gRNA molecule is configured to form a second complex with the Cas9 molecule.

17. The CRISPR/Cas system of claim 16 , wherein said second targeting domain comprises a sequence that is the same as, or differs by no more than 3 nucleotides from, a targeting domain sequence selected from the group consisting of SEQ ID NOs. 304-386, 389-395, 397, 398, 457-591, 594-595, 597-600, 603, 609, 610, 613-638, 642-645, 648-652, 655, 656, 747-2777, and 2780.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2022
From: MAEDER, MORGAN L.; BUMCROT, DAVID A.; SHEN, SHEN
To: EDITAS MEDICINE, INC.
Reel/Frame 059551/0094 →
Continuity (6)
Continuation 16279941 · Feb 19, 2019
Continuation 15904269 · Feb 23, 2018
Division 14644181 · Mar 10, 2015
Provisional Application 62036576 · Aug 12, 2014
Provisional Application 61950733 · Mar 10, 2014
Related Publication 20230025279A1 · Jan 26, 2023
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