IP Library Granted Patent US 10,745,453
Granted Patent B2
US 10,745,453 · App. 16/279,576 · Granted Aug 18, 2020

Compositions and methods for enhancing visual function

Inventors: Ehud Y. Isacoff (Berkeley, CA); Michael H. Berry (Berkeley, CA); Amy Holt (Berkeley, CA); Meike Visel (El Cerrito, CA); Autoosa Salari (Berkeley, CA); John G. Flannery (Berkeley, CA); Benjamin M. Gaub (Berkeley, CA)
Assignee: The Regents of the University of California
C07K14/47A61K9/0019A61K9/0048A61K9/5138A61K9/5153A61K48/0058A61K48/0075A61K48/0083A61P27/04C12N15/85A61K38/00C12N2750/14143
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Quick Facts
Patent No.
US 10,745,453
App. No.
16/279,576
Granted
Aug 18, 2020
Kind
B2
Abstract

The present disclosure provides a method of restoring or enhancing visual function in an individual, the method comprising administering to the individual a nucleic acid comprising a nucleotide sequence encoding one or more of a medium wavelength cone opsin (MW-opsin), a long wavelength cone opsin (LW-opsin), and a short wavelength cone opsin (SW-opsin). One or more of the MW-opsin, LW-opsin, and SW-opsin is expressed in a retinal cell in the individual, thereby restoring or enhancing visual function.

Claims (26)

1. A method of restoring or enhancing visual function in an individual having retinal degeneration, the method comprising administering directly to an eye of the individual at least one recombinant expression vector comprising a nucleic acid comprising one or more of: i) a nucleotide sequence encoding a medium wavelength opsin (MW-opsin); ii) a nucleotide sequence encoding a long wavelength opsin (LW-opsin); and iii) a nucleotide sequence encoding a short wavelength opsin (SW-opsin), wherein the one or more of the nucleotide sequence encoding SW-opsin, the nucleotide sequence encoding MW-opsin, and the nucleotide sequence encoding LW-opsin are operably linked to a promoter other than an opsin promoter and are expressed in a retinal cell in the individual, thereby mediating the restoring or the enhancing visual function in the individual, wherein the retinal cell is a retinal ganglion cell, an amacrine cell, a horizontal cell, or a bipolar cell.

2. The method of claim 1 , wherein the MW-opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:1; wherein the LW-opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:4, and wherein the SW-opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:5.

3. The method of claim 1 , wherein the nucleic acid comprises the nucleotide sequence encoding SW-opsin, wherein the SW-opsin comprises an amino acid sequence having at least 98% amino acid sequence identity to the human SW-opsin amino acid sequence set forth in SEQ ID NO:5 or having at least 98% amino acid sequence identity to the mouse SW-opsin amino acid sequence set forth in SEQ ID NO:6.

4. The method of claim 1 , wherein the at least one recombinant expression vector comprises a first nucleic acid and a second nucleic acid, and wherein: i) the first nucleic acid comprises the nucleotide sequence encoding the SW-opsin wherein the SW-opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the human SW-opsin amino acid sequence set forth in SEQ ID NO:5; and ii) the second nucleic acid comprises the nucleotide sequence encoding the SW-opsin wherein the SW-opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the mouse SW-opsin amino acid sequence set forth in SEQ ID NO:6.

5. The method of claim 1 , wherein said restoring or said enhancing visual function comprises restoring or enhancing patterned vision and image recognition by the individual.

6. The method of claim 5 , wherein the image recognition is of a static image or a pattern.

7. The method of claim 5 , wherein the image recognition is of a moving image or a pattern.

8. The method of claim 1 , wherein said restoring or said enhancing visual function comprises restoring or enhancing image recognition at a light intensity of from about 10 −4 W/cm 2 to about 1 W/cm 2 .

9. The method of claim 1 , wherein said restoring or said enhancing visual function comprises restoring or enhancing image recognition at a light intensity that is at least 10-fold lower than the light intensity required to provide for image recognition by an individual expressing a channelrhodopsin polypeptide in a retinal cell.

10. The method of claim 1 , wherein said restoring or said enhancing visual function comprises restoring or enhancing kinetics that are at least 2-fold faster than the kinetics conferred on a retinal cell by a rhodopsin polypeptide.

11. The method of claim 1 , wherein the at least one recombinant expression vector is a recombinant viral vector.

12. The method of claim 11 , wherein the recombinant viral vector is an adeno-associated viral vector, a lentiviral vector, a herpes simplex virus vector, or a retroviral vector.

13. The method of claim 1 , wherein the nucleic acid sequence is further operably linked to a transcriptional control element that is functional in the retinal cell.

14. The method of claim 13 , wherein the transcriptional control element is a retinal cell-specific promoter.

15. The method of claim 1 , wherein the promoter is a synapsin promoter, a CAG promoter, a CMV promoter, a grm6 promoter, a Pleiades promoter, a ChAT promoter, a V-glut promoter, a GAD promoter, a PV promoter, a somatostatin (SST) promoter, a neuropeptide Y (NPY) promoter, a VIP promoter, a rhodopsin kinase promoter, a vitelliform macular dystrophy 2 (VMD2) gene promoter, or an interphotoreceptor retinoid-binding protein (IRBP) gene promoter.

16. The method of claim 1 , wherein said administering is via intraocular injection, intravitreal injection, or subretinal injection.

17. The method of claim 1 , wherein the individual has an ocular disease selected from retinitis pigmentosa, macular degeneration, retinoschisis, Leber's Congenital Amaurosis, and diabetic retinopathy.

18. The method of claim 1 , wherein the individual has experienced retinal detachment or photoreceptor loss due to trauma or head injury.

19. The method of claim 1 , wherein the retinal cell is a retinal ganglion cell.

20. The method of claim 1 , wherein the at least recombinant expression vector is a recombinant adeno-associated viral vector.

21. The method of claim 1 , wherein the individual has retinitis pigmentosa.

22. The method of claim 20 , wherein the adeno-associated viral vector is AAV2.

23. The method of claim 1 , wherein said administering is via a periocular, an intraocular, an intravitreal, a subconjunctiva, a retrobulbar, a scleral, a sub-retinal, or an intracameral route of administration.

24. The method of claim 1 , wherein the promoter is a synapsin promoter.

25. The method of claim 1 , wherein the promoter is a CAG promoter.

26. The method of claim 1 , wherein the promoter is a V-glut promoter.

Assignments (3)
CONFIRMATORY LICENSE Recorded Feb 7, 2023
From: UNIVERSITY OF CALIFORNIA BERKELEY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 062668/0504 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2020
From: BERRY, MICHAEL H.; HOLT, AMY; VISEL, MEIKE; SALARI, AUTOOSA; GAUB, BENJAMIN M; FLANNERY, JOHN G.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 053137/0348 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2019
From: ISACOFF, EHUD Y.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 049919/0076 →
Continuity (5)
Continuation PCTUS2018060669 · Nov 13, 2018
Provisional Application 62641783 · Mar 12, 2018
Provisional Application 62589476 · Nov 21, 2017
Provisional Application 62585237 · Nov 13, 2017
Related Publication 20190169244A1 · Jun 6, 2019