Granted Patent
B2
US 12,257,320 · App. 17/199,115 · Granted Mar 25, 2025
Gene therapy for NMNAT1-associated retinal degeneration
Inventors:
Eric A. Pierce (Belmont, MA); Luk H. Vandenberghe (Weston, MA); Scott Greenwald (Boston, MA); Emily Brown (Boston, MA)
Assignee:
Massachusetts Eye and Ear Infirmary
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Abstract
Methods and compositions for gene therapy of retinal degeneration related to mutations in nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1).
Claims (18)
1. A method of treating retinal degeneration caused by mutations in a nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene in a human subject, the method comprising delivering to an eye of the subject a therapeutically effective amount of an Adeno-associated virus 2/9 (AAV2/9) vector comprising a sequence encoding a functional human NMNAT1, operably linked to a CASI promoter that drives expression in photoreceptors, wherein the sequence encoding the functional human NMNAT1 is at least 98% identical to SEQ ID NO: 1.
2. The method of claim 1 , wherein the sequence encoding the functional human NMNAT1 is codon optimized.
3. The method of claim 1 , wherein the vector is delivered via sub-retinal injection.
4. The method of claim 1 , wherein the vector is self-complementary AAV2/9 (scAAV2/9).
5. The method of claim 1 , wherein the sequence encoding the functional human NMNAT1 is at least 99% identical to SEQ ID NO: 1.
6. The method of claim 1 , wherein the sequence encoding the functional human NMNAT1 comprises SEQ ID NO:1.
7. The method of claim 1 , wherein the vector further comprises a 3′ bovine growth hormone untranslated region.
8. A method of increasing expression of NMNAT1 in photoreceptor cells in an eye of a human subject, the method comprising delivering to the eye of the subject a therapeutically effective amount of an Adeno-associated virus type 2/9 (AAV2/9) vector comprising a sequence encoding a functional human NMNAT1, operably linked to a CASI promoter that drives expression in the photoreceptor cells, wherein the subject has retinal degeneration caused by a mutation in a nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene, wherein the sequence encoding the functional human NMNAT1 is at least 97% identical to SEQ ID NO: 1.
9. The method of claim 8 , wherein the vector is delivered via sub-retinal injection.
10. The method of claim 8 , wherein the vector is self-complementary AAV2/9 (scAAV2/9).
11. The method of claim 8 , wherein the sequence encoding the functional human NMNAT1 is at least 98% identical to SEQ ID NO:1.
12. The method of claim 8 , wherein the sequence encoding the functional human NMNAT1 is at least 99% identical to SEQ ID NO: 1.
13. The method of claim 8 , wherein the sequence encoding the functional human NMNAT1 comprises SEQ ID NO:1.
14. An Adeno-associated virus type 2/9 (AAV2/9) vector comprising a sequence encoding a functional human NMNAT1, operably linked to a CASI promotor that drives expression in photoreceptor cells, wherein the sequence encoding the functional human NMNAT1 is codon at least 98% identical to SEQ ID NO: 1.
15. The AAV2/9 vector of claim 14 , wherein the vector is a self-complementary AAV2/9 (scAAV2/9).
16. The AAV2/9 vector of claim 14 , wherein the sequence encoding the functional human NMNAT1 is at least 99% identical to SEQ ID NO:1.
17. The AAV2/9 vector of claim 14 , wherein the sequence encoding the functional human NMNAT1 comprises SEQ ID NO:1.
18. A pharmaceutical composition comprising the vector of claim 14 , formulated for delivery via sub-retinal injection.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 21, 2025
From: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.
To: MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 070284/0464 →
CONFIRMATORY LICENSE
Recorded Nov 2, 2023
From: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065431/0686 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 20, 2021
From: PIERCE, ERIC A.; GREENWALD, SCOTT; BROWN, EMILY
To: MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 056304/0965 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 7, 2021
From: VANDENBERGHE, LUK H.
To: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.; MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 056181/0184 →
Continuity (2)
Provisional Application
62988260
· Mar 11, 2020
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